Comprehensive Physiology Wiley Online Library

Innate Immune Cells and Hypertension: Neutrophils and Neutrophil Extracellular Traps (NETs)

Full Article on Wiley Online Library


Uncontrolled immune system activation amplifies end‐organ injury in hypertension. Nonetheless, the exact mechanisms initiating this exacerbated inflammatory response, thereby contributing to further increases in blood pressure (BP), are still being revealed. While participation of lymphoid‐derived immune cells has been well described in the hypertension literature, the mechanisms by which myeloid‐derived innate immune cells contribute to T cell activation, and subsequent BP elevation, remains an active area of investigation. In this article, we critically analyze the literature to understand how monocytes, macrophages, dendritic cells, and polymorphonuclear leukocytes, including mast cells, eosinophils, basophils, and neutrophils, contribute to hypertension and hypertension‐associated end‐organ injury. The most abundant leukocytes, neutrophils, are indisputably increased in hypertension. However, it is unknown how (and why) they switch from critical first responders of the innate immune system, and homeostatic regulators of BP, to tissue‐damaging, pro‐hypertensive mediators. We propose that myeloperoxidase‐derived pro‐oxidants, neutrophil elastase, neutrophil extracellular traps (NETs), and interactions with other innate and adaptive immune cells are novel mechanisms that could contribute to the inflammatory cascade in hypertension. We further posit that the gut microbiota serves as a set point for neutropoiesis and their function. Finally, given that hypertension appears to be a key risk factor for morbidity and mortality in COVID‐19 patients, we put forth evidence that neutrophils and NETs cause cardiovascular injury post‐coronavirus infection, and thus may be proposed as an intriguing therapeutic target for high‐risk individuals. © 2021 American Physiological Society. Compr Physiol 11:1575‐1589, 2021.

Keywords: immune system; myeloid‐derived immune cells; neutrophils; gut microbiota; blood pressure; oxidative stress; COVID‐19

Figure 1. Figure 1. Myeloid‐derived immune cells that make up the innate immune system include circulating monocytes, tissue‐resident macrophages, antigen‐presenting dendritic cells, and polymorphonuclear leukocytes (also termed granulocytes), such as mast cells, basophils, eosinophils, and neutrophils. Physiologically, these cells co‐exist to maintain homeostasis. For example, acute and controlled activation of these cells dictates an inflammatory milieu that attempts to contain damage, facilitate tissue repair, and direct the adaptive immune system. On the other hand, chronic and uncontrolled activation of these cells can contribute to vascular damage, including endothelial dysfunction, medial thickening, and perivascular adipose tissue inflammation. For example, one of the major functions of activated neutrophils is the expulsion of their DNA as web‐like chromatin structures termed neutrophil extracellular traps (NETs). NETs are a network of extracellular fibers comprising primarily of DNA and citrullinated histone 3 released into the extracellular space in combination with other granule proteins, including neutrophil elastase, myeloperoxidase (MPO), and cathepsin G. This expelled DNA generates a pro‐oxidative, pro‐inflammatory, and pro‐thrombotic milieu capable of inducing endothelial damage. Therefore, NETs are a novel mechanism of vascular injury in hypertension. ROS, reactive oxygen species.
Figure 2. Figure 2. Chemical reactions that make up the respiratory burst function in neutrophils via NADPH oxidase 2 (NOX2). Classically, this is a potent antimicrobial defense against an invading pathogen. Upon endocytosis of the microbe (not depicted), NOX2 produces superoxide (O2−•) from molecular oxygen (O2), and then superoxide is then subsequently converted to other ROS, like hydrogen peroxide (H2O2). In neutrophils, myeloperoxidase (MPO) converts H2O2 to hypohalous acid (HOCl). Based on Singel KL and Segal BH, 2016 194.

Figure 1. Myeloid‐derived immune cells that make up the innate immune system include circulating monocytes, tissue‐resident macrophages, antigen‐presenting dendritic cells, and polymorphonuclear leukocytes (also termed granulocytes), such as mast cells, basophils, eosinophils, and neutrophils. Physiologically, these cells co‐exist to maintain homeostasis. For example, acute and controlled activation of these cells dictates an inflammatory milieu that attempts to contain damage, facilitate tissue repair, and direct the adaptive immune system. On the other hand, chronic and uncontrolled activation of these cells can contribute to vascular damage, including endothelial dysfunction, medial thickening, and perivascular adipose tissue inflammation. For example, one of the major functions of activated neutrophils is the expulsion of their DNA as web‐like chromatin structures termed neutrophil extracellular traps (NETs). NETs are a network of extracellular fibers comprising primarily of DNA and citrullinated histone 3 released into the extracellular space in combination with other granule proteins, including neutrophil elastase, myeloperoxidase (MPO), and cathepsin G. This expelled DNA generates a pro‐oxidative, pro‐inflammatory, and pro‐thrombotic milieu capable of inducing endothelial damage. Therefore, NETs are a novel mechanism of vascular injury in hypertension. ROS, reactive oxygen species.

Figure 2. Chemical reactions that make up the respiratory burst function in neutrophils via NADPH oxidase 2 (NOX2). Classically, this is a potent antimicrobial defense against an invading pathogen. Upon endocytosis of the microbe (not depicted), NOX2 produces superoxide (O2−•) from molecular oxygen (O2), and then superoxide is then subsequently converted to other ROS, like hydrogen peroxide (H2O2). In neutrophils, myeloperoxidase (MPO) converts H2O2 to hypohalous acid (HOCl). Based on Singel KL and Segal BH, 2016 194.
 1.Abdo AI, Rayner BS, van Reyk DM, Hawkins CL. Low‐density lipoprotein modified by myeloperoxidase oxidants induces endothelial dysfunction. Redox Biol 13: 623‐632, 2017.
 2.Abi Abdallah DS, Egan CE, Butcher BA, Denkers EY. Mouse neutrophils are professional antigen‐presenting cells programmed to instruct Th1 and Th17 T‐cell differentiation. Int Immunol 23: 317‐326, 2011.
 3.Abu Nabah YN, Losada M, Estelles R, Mateo T, Company C, Piqueras L, Lopez‐Gines C, Sarau H, Cortijo J, Morcillo EJ, Jose PJ, Sanz MJ. CXCR2 blockade impairs angiotensin II‐induced CC chemokine synthesis and mononuclear leukocyte infiltration. Arterioscler Thromb Vasc Biol 27: 2370‐2376, 2007.
 4.Adnan S, Nelson JW, Ajami NJ, Venna VR, Petrosino JF, Bryan RM Jr, Durgan DJ. Alterations in the gut microbiota can elicit hypertension in rats. Physiol Genomics 49: 96‐104, 2017.
 5.Aldabbous L, Abdul‐Salam V, McKinnon T, Duluc L, Pepke‐Zaba J, Southwood M, Ainscough AJ, Hadinnapola C, Wilkins MR, Toshner M, Wojciak‐Stothard B. Neutrophil extracellular traps promote angiogenesis: Evidence from vascular pathology in pulmonary hypertension. Arterioscler Thromb Vasc Biol 36: 2078‐2087, 2016.
 6.Alfaidi M, Wilson H, Daigneault M, Burnett A, Ridger V, Chamberlain J, Francis S. Neutrophil elastase promotes interleukin‐1beta secretion from human coronary endothelium. J Biol Chem 290: 24067‐24078, 2015.
 7.Aliko A, Kaminska M, Falkowski K, Bielecka E, Benedyk‐Machaczka M, Malicki S, Koziel J, Wong A, Bryzek D, Kantyka T, Mydel P. Discovery of novel potential reversible peptidyl arginine deiminase inhibitor. Int J Mol Sci 20: 2174, 2019.
 8.Andonegui G, Bonder CS, Green F, Mullaly SC, Zbytnuik L, Raharjo E, Kubes P. Endothelium‐derived Toll‐like receptor‐4 is the key molecule in LPS‐induced neutrophil sequestration into lungs. J Clin Invest 111: 1011‐1020, 2003.
 9.Aranow C, Ginzler EM. Epidemiology of cardiovascular disease in systemic lupus erythematosus. Lupus 9: 166‐169, 2000.
 10.Arndt H, Smith CW, Granger DN. Leukocyte‐endothelial cell adhesion in spontaneously hypertensive and normotensive rats. Hypertension 21: 667‐673, 1993.
 11.Arroyo R, Khan MA, Echaide M, Perez‐Gil J, Palaniyar N. SP‐D attenuates LPS‐induced formation of human neutrophil extracellular traps (NETs), protecting pulmonary surfactant inactivation by NETs. Commun Biol 2: 470, 2019.
 12.Asagami T, Reaven GM, Tsao PS. Enhanced monocyte adherence to thoracic aortae from rats with two forms of experimental hypertension. Am J Hypertens 12: 890‐893, 1999.
 13.Baldus S, Heeschen C, Meinertz T, Zeiher AM, Eiserich JP, Munzel T, Simoons ML, Hamm CW, CAPTURE Investigators. Myeloperoxidase serum levels predict risk in patients with acute coronary syndromes. Circulation 108: 1440‐1445, 2003.
 14.Baldus S, Heitzer T, Eiserich JP, Lau D, Mollnau H, Ortak M, Petri S, Goldmann B, Duchstein HJ, Berger J, Helmchen U, Freeman BA, Meinertz T, Munzel T. Myeloperoxidase enhances nitric oxide catabolism during myocardial ischemia and reperfusion. Free Radic Biol Med 37: 902‐911, 2004.
 15.Bank U, Kupper B, Reinhold D, Hoffmann T, Ansorge S. Evidence for a crucial role of neutrophil‐derived serine proteases in the inactivation of interleukin‐6 at sites of inflammation. FEBS Lett 461: 235‐240, 1999.
 16.Barbaro NR, Foss JD, Kryshtal DO, Tsyba N, Kumaresan S, Xiao L, Mernaugh RL, Itani HA, Loperena R, Chen W, Dikalov S, Titze JM, Knollmann BC, Harrison DG, Kirabo A. Dendritic cell amiloride‐sensitive channels mediate sodium‐induced inflammation and hypertension. Cell Rep 21: 1009‐1020, 2017.
 17.Barnes BJ, Adrover JM, Baxter‐Stoltzfus A, Borczuk A, Cools‐Lartigue J, Crawford JM, Dassler‐Plenker J, Guerci P, Huynh C, Knight JS, Loda M, Looney MR, McAllister F, Rayes R, Renaud S, Rousseau S, Salvatore S, Schwartz RE, Spicer JD, Yost CC, Weber A, Zuo Y, Egeblad M. Targeting potential drivers of COVID‐19: Neutrophil extracellular traps. J Exp Med 217: e20200652, 2020.
 18.Basheer M, Schwalb H, Shefler I, Levdansky L, Mekori YA, Gorodetsky R. Blood pressure modulation following activation of mast cells by cationic cell penetrating peptides. Peptides 32: 2444‐2451, 2011.
 19.Beauvillain C, Delneste Y, Scotet M, Peres A, Gascan H, Guermonprez P, Barnaba V, Jeannin P. Neutrophils efficiently cross‐prime naive T cells in vivo. Blood 110: 2965‐2973, 2007.
 20.Belen E, Sungur A, Sungur MA, Erdogan G. Increased neutrophil to lymphocyte ratio in patients with resistant hypertension. J Clin Hypertens (Greenwich) 17: 532‐537, 2015.
 21.Berezin A. Neutrophil extracellular traps: The core player in vascular complications of diabetes mellitus. Diabetes Metab Syndr 13: 3017‐3023, 2019.
 22.Binger KJ, Gebhardt M, Heinig M, Rintisch C, Schroeder A, Neuhofer W, Hilgers K, Manzel A, Schwartz C, Kleinewietfeld M, Voelkl J, Schatz V, Linker RA, Lang F, Voehringer D, Wright MD, Hubner N, Dechend R, Jantsch J, Titze J, Muller DN. High salt reduces the activation of IL‐4‐ and IL‐13‐stimulated macrophages. J Clin Invest 125: 4223‐4238, 2015.
 23.Bonaventura A, Vecchie A, Abbate A, Montecucco F. Neutrophil extracellular traps and cardiovascular diseases: An update. Cells 9: 231, 2020.
 24.Borissoff JI, Joosen IA, Versteylen MO, Brill A, Fuchs TA, Savchenko AS, Gallant M, Martinod K, Ten Cate H, Hofstra L, Crijns HJ, Wagner DD, Kietselaer B. Elevated levels of circulating DNA and chromatin are independently associated with severe coronary atherosclerosis and a prothrombotic state. Arterioscler Thromb Vasc Biol 33: 2032‐2040, 2013.
 25.Bosch X, Lozano F, Cervera R, Ramos‐Casals M, Min B. Basophils, IgE, and autoantibody‐mediated kidney disease. J Immunol 186: 6083‐6090, 2011.
 26.Brennan ML, Penn MS, Van Lente F, Nambi V, Shishehbor MH, Aviles RJ, Goormastic M, Pepoy ML, McErlean ES, Topol EJ, Nissen SE, Hazen SL. Prognostic value of myeloperoxidase in patients with chest pain. N Engl J Med 349: 1595‐1604, 2003.
 27.Brevetti G, Schiano V, Laurenzano E, Giugliano G, Petretta M, Scopacasa F, Chiariello M. Myeloperoxidase, but not C‐reactive protein, predicts cardiovascular risk in peripheral arterial disease. Eur Heart J 29: 224‐230, 2008.
 28.Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A. Neutrophil extracellular traps kill bacteria. Science 303: 1532‐1535, 2004.
 29.Carne CA, Dockerty G. Genital warts: Need to screen for coinfection. BMJ 300: 459, 1990.
 30.Carp H, Miller F, Hoidal JR, Janoff A. Potential mechanism of emphysema: Alpha 1‐proteinase inhibitor recovered from lungs of cigarette smokers contains oxidized methionine and has decreased elastase inhibitory capacity. Proc Natl Acad Sci USA 79: 2041‐2045, 1982.
 31.Chakraborty S, Mandal J, Yang T, Cheng X, Yeo JY, McCarthy CG, Wenceslau CF, Koch LG, Hill JW, Vijay‐Kumar M, Joe B. Metabolites and hypertension: Insights into hypertension as a metabolic disorder: 2019 Harriet Dustan Award. Hypertension 75: 1386‐1396, 2020.
 32.Chan CT, Sobey CG, Lieu M, Ferens D, Kett MM, Diep H, Kim HA, Krishnan SM, Lewis CV, Salimova E, Tipping P, Vinh A, Samuel CS, Peter K, Guzik TJ, Kyaw TS, Toh BH, Bobik A, Drummond GR. Obligatory role for B cells in the development of angiotensin II‐dependent hypertension. Hypertension 66: 1023‐1033, 2015.
 33.Channappanavar R, Perlman S. Pathogenic human coronavirus infections: Causes and consequences of cytokine storm and immunopathology. Semin Immunopathol 39: 529‐539, 2017.
 34.Chen AY, DeLano FA, Valdez SR, Ha JN, Shin HY, Schmid‐Schonbein GW. Receptor cleavage reduces the fluid shear response in neutrophils of the spontaneously hypertensive rat. Am J Physiol Cell Physiol 299: C1441‐C1449, 2010.
 35.Chen L, Flies DB. Molecular mechanisms of T cell co‐stimulation and co‐inhibition. Nat Rev Immunol 13: 227‐242, 2013.
 36.Chen L, Li X, Chen M, Feng Y, Xiong C. The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS‐CoV‐2. Cardiovasc Res 116: 1097‐1100, 2020.
 37.Chen YJ, Li LJ, Tang WL, Song JY, Qiu R, Li Q, Xue H, Wright JM. First‐line drugs inhibiting the renin angiotensin system versus other first‐line antihypertensive drug classes for hypertension. Cochrane Database Syst Rev 11: CD008170, 2018.
 38.Chistiakov DA, Bobryshev YV, Nikiforov NG, Elizova NV, Sobenin IA, Orekhov AN. Macrophage phenotypic plasticity in atherosclerosis: The associated features and the peculiarities of the expression of inflammatory genes. Int J Cardiol 184: 436‐445, 2015.
 39.Cho C, Nguyen A, Bryant KJ, O'Neill SG, McNeil HP. Prostaglandin D2 metabolites as a biomarker of in vivo mast cell activation in systemic mastocytosis and rheumatoid arthritis. Immun Inflamm Dis 4: 64‐69, 2016.
 40.Clarke TB, Davis KM, Lysenko ES, Zhou AY, Yu Y, Weiser JN. Recognition of peptidoglycan from the microbiota by Nod1 enhances systemic innate immunity. Nat Med 16: 228‐231, 2010.
 41.Clozel M, Kuhn H, Hefti F, Baumgartner HR. Endothelial dysfunction and subendothelial monocyte macrophages in hypertension. Effect of angiotensin converting enzyme inhibition. Hypertension 18: 132‐141, 1991.
 42.Collin M, Bigley V. Human dendritic cell subsets: An update. Immunology 154: 3‐20, 2018.
 43.Cortjens B, de Jong R, Bonsing JG, van Woensel JBM, Antonis AFG, Bem RA. Local dornase alfa treatment reduces NETs‐induced airway obstruction during severe RSV infection. Thorax 73: 578‐580, 2018.
 44.Crowley SD, Song YS, Sprung G, Griffiths R, Sparks M, Yan M, Burchette JL, Howell DN, Lin EE, Okeiyi B, Stegbauer J, Yang Y, Tharaux PL, Ruiz P. A role for angiotensin II type 1 receptors on bone marrow‐derived cells in the pathogenesis of angiotensin II‐dependent hypertension. Hypertension 55: 99‐108, 2010.
 45.Daniel C, Leppkes M, Munoz LE, Schley G, Schett G, Herrmann M. Extracellular DNA traps in inflammation, injury and healing. Nat Rev Nephrol 15: 559‐575, 2019.
 46.Dau T, Sarker RS, Yildirim AO, Eickelberg O, Jenne DE. Autoprocessing of neutrophil elastase near its active site reduces the efficiency of natural and synthetic elastase inhibitors. Nat Commun 6: 6722, 2015. Boer OJ, Li X, Teeling P, Mackaay C, Ploegmakers HJ, van der Loos CM, Daemen MJ, de Winter RJ, van der Wal AC. Neutrophils, neutrophil extracellular traps and interleukin‐17 associate with the organisation of thrombi in acute myocardial infarction. Thromb Haemost 109: 290‐297, 2013.
 48.De Ciuceis C, Amiri F, Brassard P, Endemann DH, Touyz RM, Schiffrin EL. Reduced vascular remodeling, endothelial dysfunction, and oxidative stress in resistance arteries of angiotensin II‐infused macrophage colony‐stimulating factor‐deficient mice: Evidence for a role in inflammation in angiotensin‐induced vascular injury. Arterioscler Thromb Vasc Biol 25: 2106‐2113, 2005.
 49.Demers M, Wagner DD. Neutrophil extracellular traps: A new link to cancer‐associated thrombosis and potential implications for tumor progression. Oncoimmunology 2: e22946, 2013.
 50.Dollery CM, Owen CA, Sukhova GK, Krettek A, Shapiro SD, Libby P. Neutrophil elastase in human atherosclerotic plaques: Production by macrophages. Circulation 107: 2829‐2836, 2003.
 51.Dorffel Y, Latsch C, Stuhlmuller B, Schreiber S, Scholze S, Burmester GR, Scholze J. Preactivated peripheral blood monocytes in patients with essential hypertension. Hypertension 34: 113‐117, 1999.
 52.Doring Y, Soehnlein O, Weber C. Neutrophil extracellular traps in atherosclerosis and atherothrombosis. Circ Res 120: 736‐743, 2017.
 53.Edwards JM, Roy S, Tomcho JC, Schreckenberger ZJ, Chakraborty S, Bearss NR, Saha P, McCarthy CG, Vijay‐Kumar M, Joe B, Wenceslau CF. Microbiota are critical for vascular physiology: Germ‐free status weakens contractility and induces sex‐specific vascular remodeling in mice. Vascul Pharmacol 125‐126: 106633, 2020.
 54.Eiserich JP, Baldus S, Brennan ML, Ma W, Zhang C, Tousson A, Castro L, Lusis AJ, Nauseef WM, White CR, Freeman BA. Myeloperoxidase, a leukocyte‐derived vascular NO oxidase. Science 296: 2391‐2394, 2002.
 55.Eiserich JP, Hristova M, Cross CE, Jones AD, Freeman BA, Halliwell B, van der Vliet A. Formation of nitric oxide‐derived inflammatory oxidants by myeloperoxidase in neutrophils. Nature 391: 393‐397, 1998.
 56.El‐Benna J, Hurtado‐Nedelec M, Marzaioli V, Marie JC, Gougerot‐Pocidalo MA, Dang PM. Priming of the neutrophil respiratory burst: Role in host defense and inflammation. Immunol Rev 273: 180‐193, 2016.
 57.El‐Eshmawy MM, El‐Adawy EH, Mousa AA, Zeidan AE, El‐Baiomy AA, Abdel‐Samie ER, Saleh OM. Elevated serum neutrophil elastase is related to prehypertension and airflow limitation in obese women. BMC Womens Health 11: 1, 2011.
 58.Emoto T, Yamashita T, Kobayashi T, Sasaki N, Hirota Y, Hayashi T, So A, Kasahara K, Yodoi K, Matsumoto T, Mizoguchi T, Ogawa W, Hirata KI. Characterization of gut microbiota profiles in coronary artery disease patients using data mining analysis of terminal restriction fragment length polymorphism: Gut microbiota could be a diagnostic marker of coronary artery disease. Heart Vessels 32: 39‐46, 2017.
 59.Exner M, Minar E, Mlekusch W, Sabeti S, Amighi J, Lalouschek W, Maurer G, Bieglmayer C, Kieweg H, Wagner O, Schillinger M. Myeloperoxidase predicts progression of carotid stenosis in states of low high‐density lipoprotein cholesterol. J Am Coll Cardiol 47: 2212‐2218, 2006.
 60.Fabbiano S, Menacho‐Marquez M, Robles‐Valero J, Pericacho M, Matesanz‐Marin A, Garcia‐Macias C, Sevilla MA, Montero MJ, Alarcon B, Lopez‐Novoa JM, Martin P, Bustelo XR. Immunosuppression‐independent role of regulatory T cells against hypertension‐driven renal dysfunctions. Mol Cell Biol 35: 3528‐3546, 2015.
 61.Fang J, Ma L, Zhang S, Fang Y, Su P, Ma H. Association of myeloperoxidase gene variation with carotid atherosclerosis in patients with essential hypertension. Mol Med Rep 7: 313‐317, 2013.
 62.Faraco G, Sugiyama Y, Lane D, Garcia‐Bonilla L, Chang H, Santisteban MM, Racchumi G, Murphy M, Van Rooijen N, Anrather J, Iadecola C. Perivascular macrophages mediate the neurovascular and cognitive dysfunction associated with hypertension. J Clin Invest 126: 4674‐4689, 2016.
 63.Ferrante CJ, Pinhal‐Enfield G, Elson G, Cronstein BN, Hasko G, Outram S, Leibovich SJ. The adenosine‐dependent angiogenic switch of macrophages to an M2‐like phenotype is independent of interleukin‐4 receptor alpha (IL‐4Ralpha) signaling. Inflammation 36: 921‐931, 2013.
 64.Franck G, Mawson TL, Folco EJ, Molinaro R, Ruvkun V, Engelbertsen D, Liu X, Tesmenitsky Y, Shvartz E, Sukhova GK, Michel JB, Nicoletti A, Lichtman A, Wagner D, Croce KJ, Libby P. Roles of PAD4 and NETosis in experimental atherosclerosis and arterial injury: Implications for superficial erosion. Circ Res 123: 33‐42, 2018.
 65.Friedman GD, Selby JV, Quesenberry CP Jr. The leukocyte count: A predictor of hypertension. J Clin Epidemiol 43: 907‐911, 1990.
 66.Fuchs TA, Abed U, Goosmann C, Hurwitz R, Schulze I, Wahn V, Weinrauch Y, Brinkmann V, Zychlinsky A. Novel cell death program leads to neutrophil extracellular traps. J Cell Biol 176: 231‐241, 2007.
 67.Futosi K, Fodor S, Mocsai A. Neutrophil cell surface receptors and their intracellular signal transduction pathways. Int Immunopharmacol 17: 638‐650, 2013.
 68.Galla S, Chakraborty S, Cheng X, Yeo JY, Mell B, Chiu N, Wenceslau CF, Vijay‐Kumar M, Joe B. Exposure to amoxicillin in early life is associated with changes in gut microbiota and reduction in blood pressure: Findings from a study on rat dams and offspring. J Am Heart Assoc 9: e014373, 2020.
 69.Gasser O, Hess C, Miot S, Deon C, Sanchez JC, Schifferli JA. Characterisation and properties of ectosomes released by human polymorphonuclear neutrophils. Exp Cell Res 285: 243‐257, 2003.
 70.Gauckler P, Shin JI, Mayer G, Kronbichler A. Eosinophilia and kidney disease: More than just an incidental finding? J Clin Med 7: 529, 2018.
 71.Golonka RM, Saha P, Yeoh BS, Chattopadhyay S, Gewirtz AT, Joe B, Vijay‐Kumar M. Harnessing innate immunity to eliminate SARS‐CoV‐2 and ameliorate COVID‐19 disease. Physiol Genomics 52: 217‐221, 2020.
 72.Groutas WC, Dou D, Alliston KR. Neutrophil elastase inhibitors. Expert Opin Ther Pat 21: 339‐354, 2011.
 73.Guo T, Fan Y, Chen M, Wu X, Zhang L, He T, Wang H, Wan J, Wang X, Lu Z. Cardiovascular implications of fatal outcomes of patients with Coronavirus Disease 2019 (COVID‐19). JAMA Cardiol 5: 811‐818, 2020.
 74.Guzik TJ, Hoch NE, Brown KA, McCann LA, Rahman A, Dikalov S, Goronzy J, Weyand C, Harrison DG. Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J Exp Med 204: 2449‐2460, 2007.
 75.Haller H, Behrend M, Park JK, Schaberg T, Luft FC, Distler A. Monocyte infiltration and c‐fms expression in hearts of spontaneously hypertensive rats. Hypertension 25: 132‐138, 1995.
 76.Hanff TC, Harhay MO, Brown TS, Cohen JB, Mohareb AM. Is there an association between COVID‐19 mortality and the renin‐angiotensin system – a call for epidemiologic investigations. Clin Infect Dis 71: 870‐874, 2020.
 77.Hansen PR. Role of neutrophils in myocardial ischemia and reperfusion. Circulation 91: 1872‐1885, 1995.
 78.Hartner A, Porst M, Gauer S, Prols F, Veelken R, Hilgers KF. Glomerular osteopontin expression and macrophage infiltration in glomerulosclerosis of DOCA‐salt rats. Am J Kidney Dis 38: 153‐164, 2001.
 79.Harwani SC. Macrophages under pressure: The role of macrophage polarization in hypertension. Transl Res 191: 45‐63, 2018.
 80.Harwani SC, Ratcliff J, Sutterwala FS, Ballas ZK, Meyerholz DK, Chapleau MW, Abboud FM. Nicotine mediates CD161a+ renal macrophage infiltration and premature hypertension in the spontaneously hypertensive rat. Circ Res 119: 1101‐1115, 2016.
 81.Hilgers KF, Hartner A, Porst M, Mai M, Wittmann M, Hugo C, Ganten D, Geiger H, Veelken R, Mann JF. Monocyte chemoattractant protein‐1 and macrophage infiltration in hypertensive kidney injury. Kidney Int 58: 2408‐2419, 2000.
 82.Hofbauer T, Scherz T, Müller J, Heidari H, Staier N, Panzenböck A, Mangold A, Lang IM. Arterial hypertension enhances neutrophil extracellular trap formation via an angiotensin‐II‐dependent pathway. Atherosclerosis 263: e67‐e68, 2017.
 83.Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 395: 497‐506, 2020.
 84.Huang L, Wang A, Hao Y, Li W, Liu C, Yang Z, Zheng F, Zhou MS. Macrophage depletion lowered blood pressure and attenuated hypertensive renal injury and fibrosis. Front Physiol 9: 473, 2018.
 85.Ihara M, Urata H, Kinoshita A, Suzumiya J, Sasaguri M, Kikuchi M, Ideishi M, Arakawa K. Increased chymase‐dependent angiotensin II formation in human atherosclerotic aorta. Hypertension 33: 1399‐1405, 1999.
 86.Ishibashi M, Hiasa K, Zhao Q, Inoue S, Ohtani K, Kitamoto S, Tsuchihashi M, Sugaya T, Charo IF, Kura S, Tsuzuki T, Ishibashi T, Takeshita A, Egashira K. Critical role of monocyte chemoattractant protein‐1 receptor CCR2 on monocytes in hypertension‐induced vascular inflammation and remodeling. Circ Res 94: 1203‐1210, 2004.
 87.Itani HA, Xiao L, Saleh MA, Wu J, Pilkinton MA, Dale BL, Barbaro NR, Foss JD, Kirabo A, Montaniel KR, Norlander AE, Chen W, Sato R, Navar LG, Mallal SA, Madhur MS, Bernstein KE, Harrison DG. CD70 exacerbates blood pressure elevation and renal damage in response to repeated hypertensive stimuli. Circ Res 118: 1233‐1243, 2016.
 88.Ito BR, Schmid‐Schonbein G, Engler RL. Effects of leukocyte activation on myocardial vascular resistance. Blood Cells 16: 145‐163; discussion 163‐146, 1990.
 89.Jaeger BN, Donadieu J, Cognet C, Bernat C, Ordonez‐Rueda D, Barlogis V, Mahlaoui N, Fenis A, Narni‐Mancinelli E, Beaupain B, Bellanne‐Chantelot C, Bajenoff M, Malissen B, Malissen M, Vivier E, Ugolini S. Neutrophil depletion impairs natural killer cell maturation, function, and homeostasis. J Exp Med 209: 565‐580, 2012.
 90.Jiang HM, Wang HX, Yang H, Zeng XJ, Tang CS, Du J, Li HH. Role for granulocyte colony stimulating factor in angiotensin II‐induced neutrophil recruitment and cardiac fibrosis in mice. Am J Hypertens 26: 1224‐1233, 2013.
 91.Jimenez‐Alcazar M, Rangaswamy C, Panda R, Bitterling J, Simsek YJ, Long AT, Bilyy R, Krenn V, Renne C, Renne T, Kluge S, Panzer U, Mizuta R, Mannherz HG, Kitamura D, Herrmann M, Napirei M, Fuchs TA. Host DNases prevent vascular occlusion by neutrophil extracellular traps. Science 358: 1202‐1206, 2017.
 92.Johnson RJ, Alpers CE, Yoshimura A, Lombardi D, Pritzl P, Floege J, Schwartz SM. Renal injury from angiotensin II‐mediated hypertension. Hypertension 19: 464‐474, 1992.
 93.Karbach SH, Schonfelder T, Brandao I, Wilms E, Hormann N, Jackel S, Schuler R, Finger S, Knorr M, Lagrange J, Brandt M, Waisman A, Kossmann S, Schafer K, Munzel T, Reinhardt C, Wenzel P. Gut microbiota promote angiotensin II‐induced arterial hypertension and vascular dysfunction. J Am Heart Assoc 5: e003698, 2016.
 94.Kelm M, Feelisch M, Krebber T, Motz W, Strauer BE. Mechanisms of histamine‐induced coronary vasodilatation: H1‐receptor‐mediated release of endothelium‐derived nitric oxide. J Vasc Res 30: 132‐138, 1993.
 95.Kenny EF, Raupach B, Abu Abed U, Brinkmann V, Zychlinsky A. Dnase1‐deficient mice spontaneously develop a systemic lupus erythematosus‐like disease. Eur J Immunol 49: 590‐599, 2019.
 96.Khalesi S, Sun J, Buys N, Jayasinghe R. Effect of probiotics on blood pressure: A systematic review and meta‐analysis of randomized, controlled trials. Hypertension 64: 897‐903, 2014.
 97.Kim YM, Haghighat L, Spiekerkoetter E, Sawada H, Alvira CM, Wang L, Acharya S, Rodriguez‐Colon G, Orton A, Zhao M, Rabinovitch M. Neutrophil elastase is produced by pulmonary artery smooth muscle cells and is linked to neointimal lesions. Am J Pathol 179: 1560‐1572, 2011.
 98.Kirabo A, Fontana V, de Faria AP, Loperena R, Galindo CL, Wu J, Bikineyeva AT, Dikalov S, Xiao L, Chen W, Saleh MA, Trott DW, Itani HA, Vinh A, Amarnath V, Amarnath K, Guzik TJ, Bernstein KE, Shen XZ, Shyr Y, Chen SC, Mernaugh RL, Laffer CL, Elijovich F, Davies SS, Moreno H, Madhur MS, Roberts J 2nd, Harrison DG. DC isoketal‐modified proteins activate T cells and promote hypertension. J Clin Invest 124: 4642‐4656, 2014.
 99.Knight JS, Luo W, O'Dell AA, Yalavarthi S, Zhao W, Subramanian V, Guo C, Grenn RC, Thompson PR, Eitzman DT, Kaplan MJ. Peptidylarginine deiminase inhibition reduces vascular damage and modulates innate immune responses in murine models of atherosclerosis. Circ Res 114: 947‐956, 2014.
 100.Knight JS, Zhao W, Luo W, Subramanian V, O'Dell AA, Yalavarthi S, Hodgin JB, Eitzman DT, Thompson PR, Kaplan MJ. Peptidylarginine deiminase inhibition is immunomodulatory and vasculoprotective in murine lupus. J Clin Invest 123: 2981‐2993, 2013.
 101.Knuckley B, Luo Y, Thompson PR. Profiling Protein Arginine Deiminase 4 (PAD4): A novel screen to identify PAD4 inhibitors. Bioorg Med Chem 16: 739‐745, 2008.
 102.Kobayashi Y. Neutrophil biology: An update. EXCLI J 14: 220‐227, 2015.
 103.Kochanek PM, Hallenbeck JM. Polymorphonuclear leukocytes and monocytes/macrophages in the pathogenesis of cerebral ischemia and stroke. Stroke 23: 1367‐1379, 1992.
 104.Kochi AN, Tagliari AP, Forleo GB, Fassini GM, Tondo C. Cardiac and arrhythmic complications in patients with COVID‐19. J Cardiovasc Electrophysiol 31: 1003‐1008, 2020.
 105.Kolck UW, Haenisch B, Molderings GJ. Cardiovascular symptoms in patients with systemic mast cell activation disease. Transl Res 174: 23‐32.e1, 2016.
 106.Kossmann S, Schwenk M, Hausding M, Karbach SH, Schmidgen MI, Brandt M, Knorr M, Hu H, Kroller‐Schon S, Schonfelder T, Grabbe S, Oelze M, Daiber A, Munzel T, Becker C, Wenzel P. Angiotensin II‐induced vascular dysfunction depends on interferon‐gamma‐driven immune cell recruitment and mutual activation of monocytes and NK‐cells. Arterioscler Thromb Vasc Biol 33: 1313‐1319, 2013.
 107.Kristal B, Shurtz‐Swirski R, Chezar J, Manaster J, Levy R, Shapiro G, Weissman I, Shasha SM, Sela S. Participation of peripheral polymorphonuclear leukocytes in the oxidative stress and inflammation in patients with essential hypertension. Am J Hypertens 11: 921‐928, 1998.
 108.Kuzeytemiz M, Demir M, Şentürk M. The relationship between eosinophil and nondipper hypertension. Cor et Vasa 55: e487‐e491, 2013.
 109.Lande R, Ganguly D, Facchinetti V, Frasca L, Conrad C, Gregorio J, Meller S, Chamilos G, Sebasigari R, Riccieri V, Bassett R, Amuro H, Fukuhara S, Ito T, Liu YJ, Gilliet M. Neutrophils activate plasmacytoid dendritic cells by releasing self‐DNA‐peptide complexes in systemic lupus erythematosus. Sci Transl Med 3: 73ra19, 2011.
 110.Lau D, Baldus S. Myeloperoxidase and its contributory role in inflammatory vascular disease. Pharmacol Ther 111: 16‐26, 2006.
 111.Lee KH, Kronbichler A, Park DD, Park Y, Moon H, Kim H, Choi JH, Choi Y, Shim S, Lyu IS, Yun BH, Han Y, Lee D, Lee SY, Yoo BH, Lee KH, Kim TL, Kim H, Shim JS, Nam W, So H, Choi S, Lee S, Shin JI. Neutrophil extracellular traps (NETs) in autoimmune diseases: A comprehensive review. Autoimmun Rev 16: 1160‐1173, 2017.
 112.Levick SP, McLarty JL, Murray DB, Freeman RM, Carver WE, Brower GL. Cardiac mast cells mediate left ventricular fibrosis in the hypertensive rat heart. Hypertension 53: 1041‐1047, 2009.
 113.Levick SP, Murray DB, Janicki JS, Brower GL. Sympathetic nervous system modulation of inflammation and remodeling in the hypertensive heart. Hypertension 55: 270‐276, 2010.
 114.Lewis HD, Liddle J, Coote JE, Atkinson SJ, Barker MD, Bax BD, Bicker KL, Bingham RP, Campbell M, Chen YH, Chung CW, Craggs PD, Davis RP, Eberhard D, Joberty G, Lind KE, Locke K, Maller C, Martinod K, Patten C, Polyakova O, Rise CE, Rudiger M, Sheppard RJ, Slade DJ, Thomas P, Thorpe J, Yao G, Drewes G, Wagner DD, Thompson PR, Prinjha RK, Wilson DM. Inhibition of PAD4 activity is sufficient to disrupt mouse and human NET formation. Nat Chem Biol 11: 189‐191, 2015.
 115.Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI. Obesity alters gut microbial ecology. Proc Natl Acad Sci USA 102: 11070‐11075, 2005.
 116.Ley RE, Turnbaugh PJ, Klein S, Gordon JI. Microbial ecology: Human gut microbes associated with obesity. Nature 444: 1022‐1023, 2006.
 117.Li J, Zhao F, Wang Y, Chen J, Tao J, Tian G, Wu S, Liu W, Cui Q, Geng B, Zhang W, Weldon R, Auguste K, Yang L, Liu X, Chen L, Yang X, Zhu B, Cai J. Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome 5: 14, 2017.
 118.Li RHL, Ng G, Tablin F. Lipopolysaccharide‐induced neutrophil extracellular trap formation in canine neutrophils is dependent on histone H3 citrullination by peptidylarginine deiminase. Vet Immunol Immunopathol 193‐194: 29‐37, 2017.
 119.Liao TD, Yang XP, Liu YH, Shesely EG, Cavasin MA, Kuziel WA, Pagano PJ, Carretero OA. Role of inflammation in the development of renal damage and dysfunction in angiotensin II‐induced hypertension. Hypertension 52: 256‐263, 2008.
 120.Liu J, Li S, Liu J, Liang B, Wang X, Wang H, Li W, Tong Q, Yi J, Zhao L, Xiong L, Guo C, Tian J, Luo J, Yao J, Pang R, Shen H, Peng C, Liu T, Zhang Q, Wu J, Xu L, Lu S, Wang B, Weng Z, Han C, Zhu H, Zhou R, Zhou H, Chen X, Ye P, Zhu B, Wang L, Zhou W, He S, He Y, Jie S, Wei P, Zhang J, Lu Y, Wang W, Zhang L, Li L, Zhou F, Wang J, Dittmer U, Lu M, Hu Y, Yang D, Zheng X. Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS‐CoV‐2 infected patients. EBioMedicine 55: 102763, 2020.
 121.Liu PP, Blet A, Smyth D, Li H. The science underlying COVID‐19: Implications for the cardiovascular system. Circulation 142: 68‐78, 2020.
 122.Liu S, Su X, Pan P, Zhang L, Hu Y, Tan H, Wu D, Liu B, Li H, Li H, Li Y, Dai M, Li Y, Hu C, Tsung A. Neutrophil extracellular traps are indirectly triggered by lipopolysaccharide and contribute to acute lung injury. Sci Rep 6: 37252, 2016.
 123.Liu X, Zhang Q, Wu H, Du H, Liu L, Shi H, Wang C, Xia Y, Guo X, Li C, Bao X, Su Q, Sun S, Wang X, Zhou M, Jia Q, Zhao H, Song K, Niu K. Blood neutrophil to lymphocyte ratio as a predictor of hypertension. Am J Hypertens 28: 1339‐1346, 2015.
 124.Liu Y, Jacobowitz DM, Barone F, McCarron R, Spatz M, Feuerstein G, Hallenbeck JM, Siren AL. Quantitation of perivascular monocytes and macrophages around cerebral blood vessels of hypertensive and aged rats. J Cereb Blood Flow Metab 14: 348‐352, 1994.
 125.Love DT, Barrett TJ, White MY, Cordwell SJ, Davies MJ, Hawkins CL. Cellular targets of the myeloperoxidase‐derived oxidant hypothiocyanous acid (HOSCN) and its role in the inhibition of glycolysis in macrophages. Free Radic Biol Med 94: 88‐98, 2016.
 126.Lozupone CA, Stombaugh JI, Gordon JI, Jansson JK, Knight R. Diversity, stability and resilience of the human gut microbiota. Nature 489: 220‐230, 2012.
 127.Lundberg K, Rydnert F, Greiff L, Lindstedt M. Human blood dendritic cell subsets exhibit discriminative pattern recognition receptor profiles. Immunology 142: 279‐288, 2014.
 128.Luo Y, Arita K, Bhatia M, Knuckley B, Lee YH, Stallcup MR, Sato M, Thompson PR. Inhibitors and inactivators of protein arginine deiminase 4: Functional and structural characterization. Biochemistry 45: 11727‐11736, 2006.
 129.Luo Y, Knuckley B, Lee YH, Stallcup MR, Thompson PR. A fluoroacetamidine‐based inactivator of protein arginine deiminase 4: Design, synthesis, and in vitro and in vivo evaluation. J Am Chem Soc 128: 1092‐1093, 2006.
 130.Mack M, Rosenkranz AR. Basophils and mast cells in renal injury. Kidney Int 76: 1142‐1147, 2009.
 131.Marques FZ, Nelson E, Chu PY, Horlock D, Fiedler A, Ziemann M, Tan JK, Kuruppu S, Rajapakse NW, El‐Osta A, Mackay CR, Kaye DM. High‐fiber diet and acetate supplementation change the gut microbiota and prevent the development of hypertension and heart failure in hypertensive mice. Circulation 135: 964‐977, 2017.
 132.Martin‐Fernandez B, Rubio‐Navarro A, Cortegano I, Ballesteros S, Alia M, Cannata‐Ortiz P, Olivares‐Alvaro E, Egido J, de Andres B, Gaspar ML, de Las HN, Lahera V, Moreno JA. Aldosterone induces renal fibrosis and inflammatory M1‐macrophage subtype via mineralocorticoid receptor in rats. PLoS One 11: e0145946, 2016.
 133.Masenga SK, Elijovich F, Hamooya BM, Nzala S, Kwenda G, Heimburger DC, Mutale W, Munsaka SM, Zhao S, Koethe JR, Kirabo A. Elevated eosinophils as a feature of inflammation associated with hypertension in virally suppressed people living with HIV. J Am Heart Assoc 9: e011450, 2020.
 134.McCarthy CG, Goulopoulou S, Wenceslau CF, Spitler K, Matsumoto T, Webb RC. Toll‐like receptors and damage‐associated molecular patterns: Novel links between inflammation and hypertension. Am J Physiol Heart Circ Physiol 306: H184‐H196, 2014.
 135.McCarthy CG, Wenceslau CF, Goulopoulou S, Ogbi S, Baban B, Sullivan JC, Matsumoto T, Webb RC. Circulating mitochondrial DNA and Toll‐like receptor 9 are associated with vascular dysfunction in spontaneously hypertensive rats. Cardiovasc Res 107: 119‐130, 2015.
 136.McIlroy DJ, Jarnicki AG, Au GG, Lott N, Smith DW, Hansbro PM, Balogh ZJ. Mitochondrial DNA neutrophil extracellular traps are formed after trauma and subsequent surgery. J Crit Care 29: 1133.e1‐5, 2014.
 137.Megiovanni AM, Sanchez F, Robledo‐Sarmiento M, Morel C, Gluckman JC, Boudaly S. Polymorphonuclear neutrophils deliver activation signals and antigenic molecules to dendritic cells: A new link between leukocytes upstream of T lymphocytes. J Leukoc Biol 79: 977‐988, 2006.
 138.Mell B, Jala VR, Mathew AV, Byun J, Waghulde H, Zhang Y, Haribabu B, Vijay‐Kumar M, Pennathur S, Joe B. Evidence for a link between gut microbiota and hypertension in the Dahl rat. Physiol Genomics 47: 187‐197, 2015.
 139.Mervaala EM, Muller DN, Park JK, Schmidt F, Lohn M, Breu V, Dragun D, Ganten D, Haller H, Luft FC. Monocyte infiltration and adhesion molecules in a rat model of high human renin hypertension. Hypertension 33: 389‐395, 1999.
 140.Mishra N, Nugent WH, Mahavadi S, Walsh SW. Mechanisms of enhanced vascular reactivity in preeclampsia. Hypertension 58: 867‐873, 2011.
 141.Mo P, Xing Y, Xiao Y, Deng L, Zhao Q, Wang H, Xiong Y, Cheng Z, Gao S, Liang K, Luo M, Chen T, Song S, Ma Z, Chen X, Zheng R, Cao Q, Wang F, Zhang Y, et al. Clinical characteristics of refractory COVID‐19 pneumonia in Wuhan, China. Clin Infect Dis, 2020. doi: 10.1093/cid/ciaa270.
 142.Mocsai A. Diverse novel functions of neutrophils in immunity, inflammation, and beyond. J Exp Med 210: 1283‐1299, 2013.
 143.Moller K, Posel C, Kranz A, Schulz I, Scheibe J, Didwischus N, Boltze J, Weise G, Wagner DC. Arterial hypertension aggravates innate immune responses after experimental stroke. Front Cell Neurosci 9: 461, 2015.
 144.Morton J, Coles B, Wright K, Gallimore A, Morrow JD, Terry ES, Anning PB, Morgan BP, Dioszeghy V, Kuhn H, Chaitidis P, Hobbs AJ, Jones SA, O'Donnell VB. Circulating neutrophils maintain physiological blood pressure by suppressing bacteria and IFNgamma‐dependent iNOS expression in the vasculature of healthy mice. Blood 111: 5187‐5194, 2008.
 145.Nabah YN, Mateo T, Estelles R, Mata M, Zagorski J, Sarau H, Cortijo J, Morcillo EJ, Jose PJ, Sanz MJ. Angiotensin II induces neutrophil accumulation in vivo through generation and release of CXC chemokines. Circulation 110: 3581‐3586, 2004.
 146.Narasaraju T, Yang E, Samy RP, Ng HH, Poh WP, Liew AA, Phoon MC, van Rooijen N, Chow VT. Excessive neutrophils and neutrophil extracellular traps contribute to acute lung injury of influenza pneumonitis. Am J Pathol 179: 199‐210, 2011.
 147.Natarajan N, Hori D, Flavahan S, Steppan J, Flavahan NA, Berkowitz DE, Pluznick JL. Microbial short chain fatty acid metabolites lower blood pressure via endothelial G protein‐coupled receptor 41. Physiol Genomics 48: 826‐834, 2016.
 148.Nathan CF, Murray HW, Wiebe ME, Rubin BY. Identification of interferon‐gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med 158: 670‐689, 1983.
 149.Ndrepepa G. Myeloperoxidase ‐ A bridge linking inflammation and oxidative stress with cardiovascular disease. Clin Chim Acta 493: 36‐51, 2019.
 150.Neeli I, Khan SN, Radic M. Histone deimination as a response to inflammatory stimuli in neutrophils. J Immunol 180: 1895‐1902, 2008.
 151.Nigro D, Sannomiya P, de Carvalho MH, Scivoletto R, Fortes ZB. Spontaneously hypertensive versus control rat aorta response to neutrophil‐derived factors. Hypertension 24: 728‐733, 1994.
 152.Ofosu‐Appiah W, Sfeir G, Smith D, Richard T. Neutrophil‐mediated damage to vascular endothelium in the spontaneously hypertensive rat. Clin Immunol Immunopathol 83: 293‐301, 1997.
 153.Okuda T, Grollman A. Passive transfer of autoimmune induced hypertension in the rat by lymph node cells. Tex Rep Biol Med 25: 257‐264, 1967.
 154.Olsen F. Transfer of arterial hypertension by splenic cells from DOCA‐salt hypertensive and renal hypertensive rats to normotensive recipients. Acta Pathol Microbiol Scand C 88: 1‐5, 1980.
 155.Onal EM, Afsar B, Covic A, Vaziri ND, Kanbay M. Gut microbiota and inflammation in chronic kidney disease and their roles in the development of cardiovascular disease. Hypertens Res 42: 123‐140, 2019.
 156.Oschatz C, Maas C, Lecher B, Jansen T, Bjorkqvist J, Tradler T, Sedlmeier R, Burfeind P, Cichon S, Hammerschmidt S, Muller‐Esterl W, Wuillemin WA, Nilsson G, Renne T. Mast cells increase vascular permeability by heparin‐initiated bradykinin formation in vivo. Immunity 34: 258‐268, 2011.
 157.Ou X, Liu Y, Lei X, Li P, Mi D, Ren L, Guo L, Guo R, Chen T, Hu J, Xiang Z, Mu Z, Chen X, Chen J, Hu K, Jin Q, Wang J, Qian Z. Characterization of spike glycoprotein of SARS‐CoV‐2 on virus entry and its immune cross‐reactivity with SARS‐CoV. Nat Commun 11: 1620, 2020.
 158.Oudit GY, Kassiri Z, Jiang C, Liu PP, Poutanen SM, Penninger JM, Butany J. SARS‐coronavirus modulation of myocardial ACE2 expression and inflammation in patients with SARS. Eur J Clin Invest 39: 618‐625, 2009.
 159.Palaniyandi SS, Inagaki K, Mochly‐Rosen D. Mast cells and epsilonPKC: A role in cardiac remodeling in hypertension‐induced heart failure. J Mol Cell Cardiol 45: 779‐786, 2008.
 160.Panizo A, Mindan FJ, Galindo MF, Cenarruzabeitia E, Hernandez M, Diez J. Are mast cells involved in hypertensive heart disease? J Hypertens 13: 1201‐1208, 1995.
 161.Pertiwi KR, de Boer OJ, Mackaaij C, Pabittei DR, de Winter RJ, Li X, van der Wal AC. Extracellular traps derived from macrophages, mast cells, eosinophils and neutrophils are generated in a time‐dependent manner during atherothrombosis. J Pathol 247: 505‐512, 2019.
 162.Petretto A, Bruschi M, Pratesi F, Croia C, Candiano G, Ghiggeri G, Migliorini P. Neutrophil extracellular traps (NET) induced by different stimuli: A comparative proteomic analysis. PLoS One 14: e0218946, 2019.
 163.Pluznick JL. Microbial short‐chain fatty acids and blood pressure regulation. Curr Hypertens Rep 19: 25, 2017.
 164.Pluznick JL, Protzko RJ, Gevorgyan H, Peterlin Z, Sipos A, Han J, Brunet I, Wan LX, Rey F, Wang T, Firestein SJ, Yanagisawa M, Gordon JI, Eichmann A, Peti‐Peterdi J, Caplan MJ. Olfactory receptor responding to gut microbiota‐derived signals plays a role in renin secretion and blood pressure regulation. Proc Natl Acad Sci USA 110: 4410‐4415, 2013.
 165.Puga I, Cols M, Barra CM, He B, Cassis L, Gentile M, Comerma L, Chorny A, Shan M, Xu W, Magri G, Knowles DM, Tam W, Chiu A, Bussel JB, Serrano S, Lorente JA, Bellosillo B, Lloreta J, Juanpere N, Alameda F, Baro T, de Heredia CD, Toran N, Catala A, Torrebadell M, Fortuny C, Cusi V, Carreras C, Diaz GA, Blander JM, Farber CM, Silvestri G, Cunningham‐Rundles C, Calvillo M, Dufour C, Notarangelo LD, Lougaris V, Plebani A, Casanova JL, Ganal SC, Diefenbach A, Arostegui JI, Juan M, Yague J, Mahlaoui N, Donadieu J, Chen K, Cerutti A. B cell‐helper neutrophils stimulate the diversification and production of immunoglobulin in the marginal zone of the spleen. Nat Immunol 13: 170‐180, 2011.
 166.Qi H, Yang S, Zhang L. Neutrophil extracellular traps and endothelial dysfunction in atherosclerosis and thrombosis. Front Immunol 8: 928, 2017.
 167.Rabb H, O'Meara YM, Maderna P, Coleman P, Brady HR. Leukocytes, cell adhesion molecules and ischemic acute renal failure. Kidney Int 51: 1463‐1468, 1997.
 168.Raikwar N, Braverman C, Snyder PM, Fenton RA, Meyerholz DK, Abboud FM, Harwani SC. Renal denervation and CD161a immune ablation prevent cholinergic hypertension and renal sodium retention. Am J Physiol Heart Circ Physiol 317: H517‐H530, 2019.
 169.Raizada MK, Joe B, Bryan NS, Chang EB, Dewhirst FE, Borisy GG, Galis ZS, Henderson W, Jose PA, Ketchum CJ, Lampe JW, Pepine CJ, Pluznick JL, Raj D, Seals DR, Gioscia‐Ryan RA, Tang WHW, Oh YS. Report of the National Heart, Lung, and Blood Institute Working Group on the role of microbiota in blood pressure regulation: Current status and future directions. Hypertension 70: 479‐485, 2017.
 170.Regal JF, Lillegard KE, Bauer AJ, Elmquist BJ, Loeks‐Johnson AC, Gilbert JS. Neutrophil depletion attenuates placental ischemia‐induced hypertension in the rat. PLoS One 10: e0132063, 2015.
 171.Reis e Sousa C. Activation of dendritic cells: Translating innate into adaptive immunity. Curr Opin Immunol 16: 21‐25, 2004.
 172.Rinninella E, Raoul P, Cintoni M, Franceschi F, Miggiano GAD, Gasbarrini A, Mele MC. What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases. Microorganisms 7: 14, 2019.
 173.Rocha‐Penha L, Caldeira‐Dias M, Tanus‐Santos JE, de Carvalho CR, Sandrim VC. Myeloperoxidase in hypertensive disorders of pregnancy and its relation with nitric oxide. Hypertension 69: 1173‐1180, 2017.
 174.Rosales C. Neutrophil: A cell with many roles in inflammation or several cell types? Front Physiol 9: 113, 2018.
 175.Roszer T. Understanding the mysterious M2 macrophage through activation markers and effector mechanisms. Mediators Inflamm 2015: 816460, 2015.
 176.Roth AJ, Ooi JD, Hess JJ, van Timmeren MM, Berg EA, Poulton CE, McGregor J, Burkart M, Hogan SL, Hu Y, Winnik W, Nachman PH, Stegeman CA, Niles J, Heeringa P, Kitching AR, Holdsworth S, Jennette JC. Pepathogenicity and detectability in ANCA‐associated vasculitis. J Clin Invest 123: 1773‐1783, 2013.
 177.Rudolph TK, Wipper S, Reiter B, Rudolph V, Coym A, Detter C, Lau D, Klinke A, Friedrichs K, Rau T, Pekarova M, Russ D, Knoll K, Kolk M, Schroeder B, Wegscheider K, Andresen H, Schwedhelm E, Boeger R, Ehmke H, Baldus S. Myeloperoxidase deficiency preserves vasomotor function in humans. Eur Heart J 33: 1625‐1634, 2012.
 178.Ruytinx P, Proost P, Van Damme J, Struyf S. Chemokine‐induced macrophage polarization in inflammatory conditions. Front Immunol 9: 1930, 2018.
 179.Sag CM, Schnelle M, Zhang J, Murdoch CE, Kossmann S, Protti A, Santos CXC, Sawyer G, Zhang X, Mongue‐Din H, Richards DA, Brewer AC, Prysyazhna O, Maier LS, Wenzel P, Eaton PJ, Shah AM. Distinct regulatory effects of myeloid cell and endothelial cell NAPDH oxidase 2 on blood pressure. Circulation 135: 2163‐2177, 2017.
 180.Saha P, Yeoh BS, Olvera RA, Xiao X, Singh V, Awasthi D, Subramanian BC, Chen Q, Dikshit M, Wang Y, Parent CA, Vijay‐Kumar M. Bacterial siderophores hijack neutrophil functions. J Immunol 198: 4293‐4303, 2017.
 181.Santisteban MM, Qi Y, Zubcevic J, Kim S, Yang T, Shenoy V, Cole‐Jeffrey CT, Lobaton GO, Stewart DC, Rubiano A, Simmons CS, Garcia‐Pereira F, Johnson RD, Pepine CJ, Raizada MK. Hypertension‐linked pathophysiological alterations in the gut. Circ Res 120: 312‐323, 2017.
 182.Schmid‐Schonbein GW, Seiffge D, DeLano FA, Shen K, Zweifach BW. Leukocyte counts and activation in spontaneously hypertensive and normotensive rats. Hypertension 17: 323‐330, 1991.
 183.Schultz J, Kaminker K. Myeloperoxidase of the leucocyte of normal human blood. I. Content and localization. Arch Biochem Biophys 96: 465‐467, 1962.
 184.Scuderi P, Nez PA, Duerr ML, Wong BJ, Valdez CM. Cathepsin‐G and leukocyte elastase inactivate human tumor necrosis factor and lymphotoxin. Cell Immunol 135: 299‐313, 1991.
 185.Shah TJ, Leik CE, Walsh SW. Neutrophil infiltration and systemic vascular inflammation in obese women. Reprod Sci 17: 116‐124, 2010.
 186.Shen K, DeLano FA, Zweifach BW, Schmid‐Schonbein GW. Circulating leukocyte counts, activation, and degranulation in Dahl hypertensive rats. Circ Res 76: 276‐283, 1995.
 187.Sheridan FM, Dauber IM, McMurtry IF, Lesnefsky EJ, Horwitz LD. Role of leukocytes in coronary vascular endothelial injury due to ischemia and reperfusion. Circ Res 69: 1566‐1574, 1991.
 188.Shi S, Qin M, Shen B, Cai Y, Liu T, Yang F, Gong W, Liu X, Liang J, Zhao Q, Huang H, Yang B, Huang C. Association of cardiac injury with mortality in hospitalized patients with COVID‐19 in Wuhan, China. JAMA Cardiol 5: 802‐810, 2020.
 189.Shiota N, Rysa J, Kovanen PT, Ruskoaho H, Kokkonen JO, Lindstedt KA. A role for cardiac mast cells in the pathogenesis of hypertensive heart disease. J Hypertens 21: 1935‐1944, 2003.
 190.Showell HJ, Freer RJ, Zigmond SH, Schiffmann E, Aswanikumar S, Corcoran B, Becker EL. The structure‐activity relations of synthetic peptides as chemotactic factors and inducers of lysosomal secretion for neutrophils. J Exp Med 143: 1154‐1169, 1976.
 191.Sica A, Mantovani A. Macrophage plasticity and polarization: In vivo veritas. J Clin Invest 122: 787‐795, 2012.
 192.Siedlinski M, Jozefczuk E, Xu X, Teumer A, Evangelou E, Schnabel RB, Welsh P, Maffia P, Erdmann J, Tomaszewski M, Caulfield MJ, Sattar N, Holmes MV, Guzik TJ. White blood cells and blood pressure: A Mendelian randomization study. Circulation 141: 1307‐1317, 2020.
 193.Siminiak T, Flores NA, Sheridan DJ. Neutrophil interactions with endothelium and platelets: Possible role in the development of cardiovascular injury. Eur Heart J 16: 160‐170, 1995.
 194.Singel KL, Segal BH. NOX2‐dependent regulation of inflammation. Clin Sci (Lond) 130: 479‐490, 2016.
 195.Singh V, Yeoh BS, Xiao X, Kumar M, Bachman M, Borregaard N, Joe B, Vijay‐Kumar M. Interplay between enterobactin, myeloperoxidase and lipocalin 2 regulates E. coli survival in the inflamed gut. Nat Commun 6: 7113, 2015.
 196.Siracusa MC, Kim BS, Spergel JM, Artis D. Basophils and allergic inflammation. J Allergy Clin Immunol 132: 789‐801; quiz 788, 2013.
 197.Sporri R, Joller N, Hilbi H, Oxenius A. A novel role for neutrophils as critical activators of NK cells. J Immunol 181: 7121‐7130, 2008.
 198.Stein M, Keshav S, Harris N, Gordon S. Interleukin 4 potently enhances murine macrophage mannose receptor activity: A marker of alternative immunologic macrophage activation. J Exp Med 176: 287‐292, 1992.
 199.Stevens T, Ekholm K, Granse M, Lindahl M, Kozma V, Jungar C, Ottosson T, Falk‐Hakansson H, Churg A, Wright JL, Lal H, Sanfridson A. AZD9668: Pharmacological characterization of a novel oral inhibitor of neutrophil elastase. J Pharmacol Exp Ther 339: 313‐320, 2011.
 200.Stone KD, Prussin C, Metcalfe DD. IgE, mast cells, basophils, and eosinophils. J Allergy Clin Immunol 125: S73‐S80, 2010.
 201.Sun S, Lulla A, Sioda M, Winglee K, Wu MC, Jacobs DR Jr, Shikany JM, Lloyd‐Jones DM, Launer LJ, Fodor AA, Meyer KA. Gut microbiota composition and blood pressure. Hypertension 73: 998‐1006, 2019.
 202.Suzuki K, Masawa N, Takatama M. The pathogenesis of cerebrovascular lesions in hypertensive rats. Med Electron Microsc 34: 230‐239, 2001.
 203.Svendsen UG. Evidence for an initial, thymus independent and a chronic, thymus dependent phase of DOCA and salt hypertension in mice. Acta Pathol Microbiol Scand A 84: 523‐528, 1976.
 204.Svendsen UG. The role of thymus for the development and prognosis of hypertension and hypertensive vascular disease in mice following renal infarction. Acta Pathol Microbiol Scand A 84: 235‐243, 1976.
 205.Tagami M, Yamori Y. Morphological analysis of the pathogenesis of hypertensive cerebrovascular lesions: Role of monocytes and platelets in intracerebral vessel occlusions. Jpn Circ J 52: 1351‐1356, 1988.
 206.Tai W, He L, Zhang X, Pu J, Voronin D, Jiang S, Zhou Y, Du L. Characterization of the receptor‐binding domain (RBD) of 2019 novel coronavirus: Implication for development of RBD protein as a viral attachment inhibitor and vaccine. Cell Mol Immunol 17: 613‐620, 2020.
 207.Tanaka M, Fukui M, Tomiyasu K, Akabame S, Nakano K, Yamasaki M, Hasegawa G, Oda Y, Nakamura N. Eosinophil count is positively correlated with coronary artery calcification. Hypertens Res 35: 325‐328, 2012.
 208.Tanaka M, Itoh H. Hypertension as a metabolic disorder and the novel role of the gut. Curr Hypertens Rep 21: 63, 2019.
 209.Tang WH, Kitai T, Hazen SL. Gut microbiota in cardiovascular health and disease. Circ Res 120: 1183‐1196, 2017.
 210.Taylor S, Dirir O, Zamanian RT, Rabinovitch M, Thompson AAR. The role of neutrophils and neutrophil elastase in pulmonary arterial hypertension. Front Med (Lausanne) 5: 217, 2018.
 211.Touyz RM. Reactive oxygen species, vascular oxidative stress, and redox signaling in hypertension: What is the clinical significance? Hypertension 44: 248‐252, 2004.
 212.Van Beusecum JP, Barbaro NR, McDowell Z, Aden LA, Xiao L, Pandey AK, Itani HA, Himmel LE, Harrison DG, Kirabo A. High salt activates CD11c(+) antigen‐presenting cells via SGK (serum glucocorticoid kinase) 1 to promote renal inflammation and salt‐sensitive hypertension. Hypertension 74: 555‐563, 2019.
 213.Van der Zwan LP, Scheffer PG, Dekker JM, Stehouwer CD, Heine RJ, Teerlink T. Hyperglycemia and oxidative stress strengthen the association between myeloperoxidase and blood pressure. Hypertension 55: 1366‐1372, 2010.
 214.Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, Mehra MR, Schuepbach RA, Ruschitzka F, Moch H. Endothelial cell infection and endotheliitis in COVID‐19. Lancet 395: 1417‐1418, 2020.
 215.Verdecchia P, Cavallini C, Spanevello A, Angeli F. The pivotal link between ACE2 deficiency and SARS‐CoV‐2 infection. Eur J Intern Med 76: 14‐20, 2020.
 216.Vijay‐Kumar M, Saha P, Yeoh BS, Golonka, RM, McCarthy CG, Spegele A, Abokor AA, Chakraborty S, Mell B, Koch LG, Joe B. Neutrophil extracellular traps: New players in hypertension. Hypertension 74: P1126, 2019.
 217.Vinh A, Chen W, Blinder Y, Weiss D, Taylor WR, Goronzy JJ, Weyand CM, Harrison DG, Guzik TJ. Inhibition and genetic ablation of the B7/CD28 T‐cell costimulation axis prevents experimental hypertension. Circulation 122: 2529‐2537, 2010.
 218.von Bruhl ML, Stark K, Steinhart A, Chandraratne S, Konrad I, Lorenz M, Khandoga A, Tirniceriu A, Coletti R, Kollnberger M, Byrne RA, Laitinen I, Walch A, Brill A, Pfeiler S, Manukyan D, Braun S, Lange P, Riegger J, Ware J, Eckart A, Haidari S, Rudelius M, Schulz C, Echtler K, Brinkmann V, Schwaiger M, Preissner KT, Wagner DD, Mackman N, Engelmann B, Massberg S. Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo. J Exp Med 209: 819‐835, 2012.
 219.Wadman M, Couzin‐Frankel J, Kaiser J, Matacic C. How does coronavirus kill? Clinicians trace a ferocious rampage through the body, from brain to toes. Science, 2020. doi: 10.1126/science.abc3208
 220.Walls AC, Park YJ, Tortorici MA, Wall A, McGuire AT, Veesler D. Structure, function, and antigenicity of the SARS‐CoV‐2 spike glycoprotein. Cell 181: 281‐292.e6, 2020.
 221.Wang CJ, Ng CY, Brook RH. Response to COVID‐19 in Taiwan: Big Data analytics, new technology, and proactive testing. JAMA 323: 1341‐1342, 2020.
 222.Wang H, Li T, Chen S, Gu Y, Ye S. Neutrophil extracellular trap mitochondrial DNA and its autoantibody in systemic lupus erythematosus and a proof‐of‐concept trial of metformin. Arthritis Rheumatol 67: 3190‐3200, 2015.
 223.Wang LX, Zhang SX, Wu HJ, Rong XL, Guo J. M2b macrophage polarization and its roles in diseases. J Leukoc Biol 106: 345‐358, 2019.
 224.Welker P, Kramer S, Groneberg DA, Neumayer HH, Bachmann S, Amann K, Peters H. Increased mast cell number in human hypertensive nephropathy. Am J Physiol Renal Physiol 295: F1103‐F1109, 2008.
 225.Wenceslau CF, McCarthy CG, Szasz T, Goulopoulou S, Webb RC. Mitochondrial N‐formyl peptides induce cardiovascular collapse and sepsis‐like syndrome. Am J Physiol Heart Circ Physiol 308: H768‐H777, 2015.
 226.Weng M, Baron DM, Bloch KD, Luster AD, Lee JJ, Medoff BD. Eosinophils are necessary for pulmonary arterial remodeling in a mouse model of eosinophilic inflammation‐induced pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 301: L927‐L936, 2011.
 227.Wenstedt EF, Verberk SG, Kroon J, Neele AE, Baardman J, Claessen N, Pasaoglu OT, Rademaker E, Schrooten EM, Wouda RD, de Winther MP, Aten J, Vogt L, Van den Bossche J. Salt increases monocyte CCR2 expression and inflammatory responses in humans. JCI Insight 4: e130508, 2019.
 228.Wenzel P, Knorr M, Kossmann S, Stratmann J, Hausding M, Schuhmacher S, Karbach SH, Schwenk M, Yogev N, Schulz E, Oelze M, Grabbe S, Jonuleit H, Becker C, Daiber A, Waisman A, Munzel T. Lysozyme M‐positive monocytes mediate angiotensin II‐induced arterial hypertension and vascular dysfunction. Circulation 124: 1370‐1381, 2011.
 229.White FN, Grollman A. Autoimmune factors associated with infarction of the kidney. Nephron 1: 93‐102, 1964.
 230.Wilck N, Matus MG, Kearney SM, Olesen SW, Forslund K, Bartolomaeus H, Haase S, Mahler A, Balogh A, Marko L, Vvedenskaya O, Kleiner FH, Tsvetkov D, Klug L, Costea PI, Sunagawa S, Maier L, Rakova N, Schatz V, Neubert P, Fratzer C, Krannich A, Gollasch M, Grohme DA, Corte‐Real BF, Gerlach RG, Basic M, Typas A, Wu C, Titze JM, Jantsch J, Boschmann M, Dechend R, Kleinewietfeld M, Kempa S, Bork P, Linker RA, Alm EJ, Muller DN. Salt‐responsive gut commensal modulates TH17 axis and disease. Nature 551: 585‐589, 2017.
 231.Wirtz PH, von Kanel R, Frey K, Ehlert U, Fischer JE. Glucocorticoid sensitivity of circulating monocytes in essential hypertension. Am J Hypertens 17: 489‐494, 2004.
 232.Withers SB, Forman R, Meza‐Perez S, Sorobetea D, Sitnik K, Hopwood T, Lawrence CB, Agace WW, Else KJ, Heagerty AM, Svensson‐Frej M, Cruickshank SM. Eosinophils are key regulators of perivascular adipose tissue and vascular functionality. Sci Rep 7: 44571, 2017.
 233.Wright JL, Farmer SG, Churg A. A neutrophil elastase inhibitor reduces cigarette smoke‐induced remodelling of lung vessels. Eur Respir J 22: 77‐81, 2003.
 234.Wu D, Molofsky AB, Liang HE, Ricardo‐Gonzalez RR, Jouihan HA, Bando JK, Chawla A, Locksley RM. Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 332: 243‐247, 2011.
 235.Wu Y, Li Y, Zhang C, Xi A, Wang Y, Cui W, Li H, Du J. S100a8/a9 released by CD11b+Gr1+ neutrophils activates cardiac fibroblasts to initiate angiotensin II‐Induced cardiac inflammation and injury. Hypertension 63: 1241‐1250, 2014.
 236.Wynn TA, Chawla A, Pollard JW. Macrophage biology in development, homeostasis and disease. Nature 496: 445‐455, 2013.
 237.Xiao L, Kirabo A, Wu J, Saleh MA, Zhu L, Wang F, Takahashi T, Loperena R, Foss JD, Mernaugh RL, Chen W, Roberts J 2nd, Osborn JW, Itani HA, Harrison DG. Renal denervation prevents immune cell activation and renal inflammation in angiotensin II‐induced hypertension. Circ Res 117: 547‐557, 2015.
 238.Yan R, Zhang Y, Li Y, Xia L, Guo Y, Zhou Q. Structural basis for the recognition of SARS‐CoV‐2 by full‐length human ACE2. Science 367: 1444‐1448, 2020.
 239.Yang T, Chakraborty S, Saha P, Mell B, Cheng X, Yeo JY, Mei X, Zhou G, Mandal J, Golonka R, Yeoh BS, Putluri V, Piyarathna DWB, Putluri N, McCarthy CG, Wenceslau CF, Sreekumar A, Gewirtz A, Vijay‐Kumar M, Joe B. Gnotobiotic rats reveal that gut microbiota regulates colonic mRNA of Ace2, the receptor for SARS‐CoV‐2 infectivity. Hypertension 76: e1‐e3, 2020.
 240.Yang T, Santisteban MM, Rodriguez V, Li E, Ahmari N, Carvajal JM, Zadeh M, Gong M, Qi Y, Zubcevic J, Sahay B, Pepine CJ, Raizada MK, Mohamadzadeh M. Gut dysbiosis is linked to hypertension. Hypertension 65: 1331‐1340, 2015.
 241.Yao W, Chen J, Wu S, Han X, Guan J, Yuan D, Cai J, Hei Z. ONO‐5046 suppresses reactive oxidative species‐associated formation of neutrophil extracellular traps. Life Sci 210: 243‐250, 2018.
 242.Yao Y, Xu XH, Jin L. Macrophage polarization in physiological and pathological pregnancy. Front Immunol 10: 792, 2019.
 243.Yasmin, CM ME, Wallace S, Dakham Z, Pulsalkar P, Maki‐Petaja K, Ashby MJ, Cockcroft JR, Wilkinson IB. Matrix metalloproteinase‐9 (MMP‐9), MMP‐2, and serum elastase activity are associated with systolic hypertension and arterial stiffness. Arterioscler Thromb Vasc Biol 25: 372, 2005.
 244.Yeap WH, Wong KL, Shimasaki N, Teo EC, Quek JK, Yong HX, Diong CP, Bertoletti A, Linn YC, Wong SC. CD16 is indispensable for antibody‐dependent cellular cytotoxicity by human monocytes. Sci Rep 6: 34310, 2016.
 245.Yoshida N, Yamashita T, Hirata KI. Gut microbiome and cardiovascular diseases. Diseases 6: 56, 2018.
 246.Zaldivia MT, Rivera J, Hering D, Marusic P, Sata Y, Lim B, Eikelis N, Lee R, Lambert GW, Esler MD, Htun NM, Duval J, Hammond L, Eisenhardt SU, Flierl U, Schlaich MP, Peter K. Renal denervation reduces monocyte activation and monocyte‐platelet aggregate formation: An anti‐inflammatory effect relevant for cardiovascular risk. Hypertension 69: 323‐331, 2017.
 247.Zeng F, Li L, Zeng J, Deng Y, Huang H, Chen B, Deng G. Can we predict the severity of COVID‐19 with a routine blood test? Pol Arch Intern Med 7: e32628, 2020.
 248.Zhang J, Shi GP. Mast cells and metabolic syndrome. Biochim Biophys Acta 1822: 14‐20, 2012.
 249.Zhao Z, Ni Y, Chen J, Zhong J, Yu H, Xu X, He H, Yan Z, Scholze A, Liu D, Zhu Z, Tepel M. Increased migration of monocytes in essential hypertension is associated with increased transient receptor potential channel canonical type 3 channels. PLoS One 7: e32628, 2012.
 250.Zheng YY, Ma YT, Zhang JY, Xie X. COVID‐19 and the cardiovascular system. Nat Rev Cardiol 17: 259‐260, 2020.
 251.Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID‐19 in Wuhan, China: A retrospective cohort study. Lancet 395: 1054‐1062, 2020.
 252.Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579: 270‐273, 2020.
 253.Zhou X, Li J, Guo J, Geng B, Ji W, Zhao Q, Li J, Liu X, Liu J, Guo Z, Cai W, Ma Y, Ren D, Miao J, Chen S, Zhang Z, Chen J, Zhong J, Liu W, Zou M, Li Y, Cai J. Gut‐dependent microbial translocation induces inflammation and cardiovascular events after ST‐elevation myocardial infarction. Microbiome 6: 66, 2018.
 254.Zizzo G, Hilliard BA, Monestier M, Cohen PL. Efficient clearance of early apoptotic cells by human macrophages requires M2c polarization and MerTK induction. J Immunol 189: 3508‐3520, 2012.
 255.Zuo Y, Yalavarthi S, Shi H, Gockman K, Zuo M, Madison JA, Blair CN, Weber A, Barnes BJ, Egeblad M, Woods RJ, Kanthi Y, Knight JS. Neutrophil extracellular traps in COVID‐19. JCI Insight 5: e138999, 2020.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite

Cameron G. McCarthy, Piu Saha, Rachel M. Golonka, Camilla F. Wenceslau, Bina Joe, Matam Vijay‐Kumar. Innate Immune Cells and Hypertension: Neutrophils and Neutrophil Extracellular Traps (NETs). Compr Physiol 2021, 11: 1575-1589. doi: 10.1002/cphy.c200020