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(Circulation Research. 2005;96:1033.)
© 2005 American Heart Association, Inc.

Editorials

Bone Morphogenetic Protein Receptor-2 and Pulmonary Arterial Hypertension

Unraveling a Riddle Inside an Enigma?

Duncan J. Stewart

From the Terrence Donnelly Research Laboratories, Division of Cardiology, St. Michael’s Hospital, Department of Medicine and McLaughlin Center for Molecular Medicine, University of Toronto.

Correspondence to Duncan J. Stewart, Dexter Hung-Cho Man Chair and Head of the Division of Cardiology, St. Michael’s Hospital, 30 Bond Street, Suite 7-081 Queen Wing, Toronto, Ontario, Canada. E-mail stewartd@smh.toronto.on.ca

See related article, pages 1053–1063

Key Words: pulmonary arterial hypertension

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Pulmonary arterial hypertension (PAH) is an intriguing condition that is characterized by dramatic changes in the structure and function of pulmonary microcirculation, particularly at the level of the distal arteriolar bed. In addition to exuberant hypertrophy of the medial smooth muscle layers, the pathological features of PAH include hypertrophy and fibrosis of the intima, and occasionally the appearance of plexiform lesions which often occur distal to regions of arterial occlusion.¹ Plexiform lesions have attracted considerable attention even though these are not necessarily present in all patients with primary or idiopathic PAH, and they are also found in patients with PAH associated with known causes such as congenital heart disease, collagen vascular disease, and so forth. Hyperproliferative endothelial cells (EC) represent an important component of these complex glomeruloid structures, and have in some cases been shown to be of monoclonal origin.² Interestingly, although increased smooth muscle cell (SMC) and EC growth may predominate in the advanced stages of disease, more recent evidence suggest that increased apoptosis and loss of pulmonary vascular endothelium may predominate at earlier stages. Indeed selection pressure created by profound EC loss may create the conditions necessary for the emergence of apoptosis resistant and hyperproliferative endothelial cell "clones."³

The discovery of heterozygous mutations of the BMPR2 gene, encoding for the bone morphogenetic protein receptor-II (BMPR-II), in a substantial proportion of patients with familial pulmonary arterial hypertension (FPAH), as well as many cases of sporadic or idiopathic disease (IPAH),^4–6 represents perhaps the single greatest advance toward an understanding of . . . [Full Text of this Article]

Related Article:

Dysfunctional Smad Signaling Contributes to Abnormal Smooth Muscle Cell Proliferation in Familial Pulmonary Arterial Hypertension

Xudong Yang, Lu Long, Mark Southwood, Nung Rudarakanchana, Paul D. Upton, Trina K. Jeffery, Carl Atkinson, Hailan Chen, Richard C. Trembath, and Nicholas W. Morrell
Circ. Res. 2005 96: 1053-1063. [Abstract] [Full Text] [PDF]

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