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Genomics and Proteomics of Pulmonary Vascular Disease

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Study of RNA and proteins in cells of both normal and diseased tissues is providing researchers with new knowledge of disease pathologies. While still in its early stages, high‐throughput expression analysis is improving our understanding of the pathogenesis of pulmonary arterial hypertension (PAH). While many studies have used microarray and proteomic analyses as “hypothesis‐generating” tools, the technologies also have potential to identify and quantify biomarkers of disease. To date, many of the published studies have examined gene expression profiles of tissue biopsies, others have utilized cells from peripheral blood. Microarray technology has been employed successfully in the investigation of a diverse array of human diseases. The potential of high‐throughput expression analysis to improve our understanding of the pathogenesis of PAH is highlighted in this review. Proteomic studies of PAH and pulmonary vascular diseases in general have been little utilized thus far. To date, such studies are few and no consistent biomarker has emerged from studies of either plasma or blood cells from idiopathic pulmonary arterial hypertension (IPAH) patients. The studies of both lung tissue and lymphocytes are perhaps more revealing and suggest that changes in the cytoskeletal machinery may play a role in the pathogenesis of idiopathic pulmonary arterial hypertension. The oncology literature has demonstrated the utility of gene microarray analysis to predict important outcomes such as response to therapy and survival. It is likely that in the near future, gene microarrays and proteomic analyses will also be employed in a pharmacogenomics approach in PAH, helping to identify the most appropriate therapies for individual patients. © 2011 American Physiological Society. Compr Physiol 1:467‐483, 2011.

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Figure 1. Figure 1.

Dendrogram and heat map of protein expression from transformed lymphocytes from affected patients, obligate individuals, and married‐in control subjects both with and without a 4‐h treatment with bone morphogenic protein‐4 (BMP‐4). The dendrogram illustrates a distinct compartmentalization in protein‐expression patterns between the three groups. No differences are found between the samples with and without treatment with BMP‐4. The differences in protein expression are clearly seen in the heat map. Expression patterns in selected proteins are visually presented as horizontal lines in an expression matrix using a relative scale ranging from −0.5 (green) to +0.5 (red). Reprinted with permission of the American Thoracic Society. Copyright © American Thoracic Society. Meyrick et al. 72. OFFICIAL JOURNAL OF THE AMERICAN THORACIC SOCIETY DIANE GERN, Publisher.

Figure 1.

Dendrogram and heat map of protein expression from transformed lymphocytes from affected patients, obligate individuals, and married‐in control subjects both with and without a 4‐h treatment with bone morphogenic protein‐4 (BMP‐4). The dendrogram illustrates a distinct compartmentalization in protein‐expression patterns between the three groups. No differences are found between the samples with and without treatment with BMP‐4. The differences in protein expression are clearly seen in the heat map. Expression patterns in selected proteins are visually presented as horizontal lines in an expression matrix using a relative scale ranging from −0.5 (green) to +0.5 (red). Reprinted with permission of the American Thoracic Society. Copyright © American Thoracic Society. Meyrick et al. 72. OFFICIAL JOURNAL OF THE AMERICAN THORACIC SOCIETY DIANE GERN, Publisher.

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Mark Geraci, Barbara Meyrick. Genomics and Proteomics of Pulmonary Vascular Disease. Compr Physiol 2011, 1: 467-483. doi: 10.1002/cphy.c100031