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Scientifica
Volume 2012 (2012), Article ID 106576, 17 pages
http://dx.doi.org/10.6064/2012/106576
Review Article

The Molecular Genetics and Cellular Mechanisms Underlying Pulmonary Arterial Hypertension

School of Life Sciences, Faculty of Science, University of Lincoln, Brayford Pool, Lincoln LN6 7TS, UK

Received 10 October 2012; Accepted 19 November 2012

Academic Editors: J. A. Castro and B. Witzenbichler

Copyright © 2012 Rajiv D. Machado. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Pulmonary arterial hypertension (PAH) is an incurable disorder clinically characterised by a sustained elevation of mean arterial pressure in the absence of systemic involvement. As the adult circulation is a low pressure, low resistance system, PAH represents a reversal to a foetal state. The small pulmonary arteries of patients exhibit luminal occlusion resultant from the uncontrolled growth of endothelial and smooth muscle cells. This vascular remodelling is comprised of hallmark defects, most notably the plexiform lesion. PAH may be familial in nature but the majority of patients present with spontaneous disease or PAH associated with other complications. In this paper, the molecular genetic basis of the disorder is discussed in detail ranging from the original identification of the major genetic contributant to PAH and moving on to current next-generation technologies that have led to the rapid identification of additional genetic risk factors. The impact of identified mutations on the cell is examined, particularly, the determination of pathways disrupted in disease and critical to pulmonary vascular maintenance. Finally, the application of research in this area to the design and development of novel treatment options for patients is addressed along with the future directions PAH research is progressing towards.