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Renal Vascular Structure and Rarefaction

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Abstract

An intact microcirculation is vital for diffusion of oxygen and nutrients and for removal of toxins of every organ and system in the human body. The functional and/or anatomical loss of microvessels is known as rarefaction, which can compromise the normal organ function and have been suggested as a possible starting point of several diseases. The purpose of this overview is to discuss the potential underlying mechanisms leading to renal microvascular rarefaction, and the potential consequences on renal function and on the progression of renal damage. Although the kidney is a special organ that receives much more blood than its metabolic needs, experimental and clinical evidence indicates that renal microvascular rarefaction is associated to prevalent cardiovascular diseases such as diabetes, hypertension, and atherosclerosis, either as cause or consequence. On the other hand, emerging experimental evidence using progenitor cells or angiogenic cytokines supports the feasibility of therapeutic interventions capable of modifying the progressive nature of microvascular rarefaction in the kidney. This overview will also attempt to discuss the potential renoprotective mechanisms of the therapeutic targeting of the renal microcirculation. © 2013 American Physiological Society. Compr Physiol 3:817‐831, 2013.

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Figure 1. Figure 1.

Schematic illustration describing the general process of microvascular (MV) rarefaction. Changes in the tissue environment and/or metabolic needs may lead to modification in vascular tone and progressive alterations in MV shape and morphology, ultimately resulting in MV irreversible damage and loss. This process accelerates MV damage and may subsequently lead to a feed‐forward deleterious mechanism.

Figure 2. Figure 2.

Section of the human kidney showing the major vessels that supply the blood flow to the kidneys and schematic representation of the microcirculation of the nephron. The figure was reproduced with permission from Guyton and Hall Textbook of Medical Physiology, 12th Edition, 2011, Elsevier.

Figure 3. Figure 3.

Schematic illustration describing the potential mechanisms of renal microvascular (MV) rarefaction and consequences on renal function and structure. Sustained MV endothelial injury (irrespective of the etiology) can lead to an imbalance between factors involved in MV repair, proliferation, and regression, leading to a progressive MV rarefaction that can deteriorate renal hemodynamics, function, and tissue damage. In turn, the progression of renal damage may further stimulate MV damage and loss (red arrows) resulting in a vicious circle. NO, nitric oxide; VEGF, vascular endothelial growth factor; HIF‐1α, hypoxia‐induced factor‐1α.

Figure 4. Figure 4.

Schematic illustration of potential targeted interventions to protect the renal microcirculation, by stimulating MV proliferation, repair, and/or reducing MV damage and loss. Majority of evidence comes from experimental studies. ACE‐I, angiotensin converting enzyme inhibitiors; ARBs, angiotensin receptor blockers; ET‐A, endothelin‐receptor A.

Figure 5. Figure 5.

(A) Representative three‐dimensional micro‐computed tomography (micro‐CT) reconstruction and quantification of the renal MV density and vascular volume fraction, and (B) representative renal protein expression and quantification of angiogenic mediators in normal, renovascular disease (RVD), and RVD + vascular endothelial growth factor (VEGF). Intrarenal VEGF therapy restored the renal expression of VEGF and angiogenic mediators and led to a significant improvement in cortical and medullary MV density compared to untreated RVD. *, P < 0.05 versus normal; †, P < 0.05 versus RVD; #, P = 0.08 versus RVD. Reproduced, with permission, from Chade et al., Am J Physiol Renal Physiol, 302: F1342–F1350, 2012.

Figure 6. Figure 6.

Representative picture showing three‐dimensional micro‐computed tomography (micro‐CT) reconstruction of the renal microvascular (MV) architecture (a), tomographically isolated microvessels (b), and renal cross sections showing MV remodeling (c, ×40) and fibrosis (d, ×20) of a kidney exposed to chronic obstruction of blood flow due to renal artery stenosis. The significant MV rarefaction (a) and remodeling (b, c) correlates with the progression of renal fibrosis (d, curved black arrow). Furthermore, the buildup of renal scarring can promotes changes in MV shape and morphology, as it could also be a source for promoters of MV regression (white arrows).



Figure 1.

Schematic illustration describing the general process of microvascular (MV) rarefaction. Changes in the tissue environment and/or metabolic needs may lead to modification in vascular tone and progressive alterations in MV shape and morphology, ultimately resulting in MV irreversible damage and loss. This process accelerates MV damage and may subsequently lead to a feed‐forward deleterious mechanism.



Figure 2.

Section of the human kidney showing the major vessels that supply the blood flow to the kidneys and schematic representation of the microcirculation of the nephron. The figure was reproduced with permission from Guyton and Hall Textbook of Medical Physiology, 12th Edition, 2011, Elsevier.



Figure 3.

Schematic illustration describing the potential mechanisms of renal microvascular (MV) rarefaction and consequences on renal function and structure. Sustained MV endothelial injury (irrespective of the etiology) can lead to an imbalance between factors involved in MV repair, proliferation, and regression, leading to a progressive MV rarefaction that can deteriorate renal hemodynamics, function, and tissue damage. In turn, the progression of renal damage may further stimulate MV damage and loss (red arrows) resulting in a vicious circle. NO, nitric oxide; VEGF, vascular endothelial growth factor; HIF‐1α, hypoxia‐induced factor‐1α.



Figure 4.

Schematic illustration of potential targeted interventions to protect the renal microcirculation, by stimulating MV proliferation, repair, and/or reducing MV damage and loss. Majority of evidence comes from experimental studies. ACE‐I, angiotensin converting enzyme inhibitiors; ARBs, angiotensin receptor blockers; ET‐A, endothelin‐receptor A.



Figure 5.

(A) Representative three‐dimensional micro‐computed tomography (micro‐CT) reconstruction and quantification of the renal MV density and vascular volume fraction, and (B) representative renal protein expression and quantification of angiogenic mediators in normal, renovascular disease (RVD), and RVD + vascular endothelial growth factor (VEGF). Intrarenal VEGF therapy restored the renal expression of VEGF and angiogenic mediators and led to a significant improvement in cortical and medullary MV density compared to untreated RVD. *, P < 0.05 versus normal; †, P < 0.05 versus RVD; #, P = 0.08 versus RVD. Reproduced, with permission, from Chade et al., Am J Physiol Renal Physiol, 302: F1342–F1350, 2012.



Figure 6.

Representative picture showing three‐dimensional micro‐computed tomography (micro‐CT) reconstruction of the renal microvascular (MV) architecture (a), tomographically isolated microvessels (b), and renal cross sections showing MV remodeling (c, ×40) and fibrosis (d, ×20) of a kidney exposed to chronic obstruction of blood flow due to renal artery stenosis. The significant MV rarefaction (a) and remodeling (b, c) correlates with the progression of renal fibrosis (d, curved black arrow). Furthermore, the buildup of renal scarring can promotes changes in MV shape and morphology, as it could also be a source for promoters of MV regression (white arrows).

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Alejandro R. Chade. Renal Vascular Structure and Rarefaction. Compr Physiol 2013, 3: 817-831. doi: 10.1002/cphy.c120012