doi: 10.1161/01.CIR.0000156326.48823.55
(Circulation. 2005;111:534-538.)
© 2005 American Heart Association, Inc.
Editorial |
Pathogenesis of Pulmonary Arterial Hypertension
The Need for Multiple Hits
From the Department of Medicine, School of Medicine, University of California-San Diego, La Jolla.
Correspondence to Dr Lewis J. Rubin, Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California-San Diego, La Jolla, CA 92037-7381. E-mail ljrubin@ucsd.edu
Key Words: Editorials • hypertension, pulmonary • genes • heart diseases, pulmonary
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Pulmonary hypertension can be classified into 4 categories: pulmonary arterial hypertension (PAH), pulmonary venous hypertension, pulmonary hypertension associated with hypoxemia, and pulmonary hypertension due to chronic thrombotic or embolic disease. PAH is a progressive and often fatal condition that predominantly affects women. Approximately 10% of patients diagnosed with PAH without a demonstrable cause have a family history of the disease and are referred to as having familial PAH (FPAH), whereas the remainder are classified as having idiopathic PAH (IPAH).
See p 607
Regardless of the initial pathogenic trigger, the elevated pulmonary arterial pressure and vascular resistance in patients with FPAH and IPAH are primarily caused by sustained pulmonary vasoconstriction, lumen obliteration of small- and medium-sized arteries and arterioles in association with the formation of plexiform lesions and in situ thrombosis, and concentric thickening of pulmonary arteries resulting from intimal fibrosis, and medial hypertrophy resulting from excessive proliferation of smooth muscle cells.1 The plexiform lesion, a histological hallmark of FPAH and IPAH, has been demonstrated to result from monoclonal proliferation of endothelial cells, migration and proliferation of smooth muscle cells, and accumulation of circulating cells (eg, macrophages, endothelial progenitor cells).1,2 These observations suggest that the pulmonary vasculature in FPAH and IPAH patients is phenotypically different from that in normal subjects because of inheritable or acquired mutations (or polymorphisms) of certain genes that are specifically involved in regulating proliferation, apoptosis, and differentiation in pulmonary arterial smooth muscle cells (PASMCs) and pulmonary arterial endothelial cells (PAECs).
The pathogenesis of PAH remains incompletely understood;
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Circulation 2005 111: 607-613.
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