Circulation. 2004;109:159-165
doi: 10.1161/01.CIR.0000102381.57477.50
doi: 10.1161/01.CIR.0000102381.57477.50
(Circulation. 2004;109:159-165.)
© 2004 American Heart Association, Inc.
Review: Current Perspectives |
Endothelial Dysfunction in Pulmonary Hypertension
From the Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Tufts—New England Medical Center, Tufts University School of Medicine, Boston, Mass (R.B.), and Division of Cardiopulmonary Pathology, Department of Pathology (R.M.T.), and Division of Pulmonary and Critical Care Medicine (P.M.H.), Department of Medicine, Johns Hopkins Hospital and Johns Hopkins University School of Medicine, Baltimore, Md.
Correspondence to Dr Paul M. Hassoun, 5501 Hopkins Bayview Circle, Baltimore, MD 21224. E-mail phassoun@jhmi.edu
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
The pathogenesis of pulmonary hypertension (PH) involves a complex and multifactorial process. Endothelial dysfunction seems to play an integral role in mediating the structural changes in the pulmonary vasculature. Disordered endothelial cell proliferation along with concurrent neoangiogenesis, when exuberant, results in the formation of glomeruloid structures known as the plexiform lesions, which are common pathological features of the pulmonary vessels of patients with pulmonary arterial hypertension (PAH). In addition, an altered production of various endothelial vasoactive mediators, such as NO, prostacyclin, endothelin-1 (ET-1), serotonin, and thromboxane, has been increasingly recognized in patients with PH. Because most of these mediators affect the growth of the smooth muscle cells, an alteration in their production may facilitate the development of pulmonary vascular hypertrophy and structural remodeling characteristic of PH. It is conceivable that the beneficial effects of many of the treatments currently available for PAH, such as the use of prostacyclin, NO, and ET antagonists, result at least in part from restoring the balance between these mediators. However, the ultimate cellular and physiological targets of these treatments remain unknown.
In addition to the potential consequences of an imbalance in the endothelial production of various mediators, injury to the endothelium may expose the underlying vascular tissue to diverse blood-borne factors that may further promote pathological changes. Endothelial dysfunction may also have adverse consequences on pulmonary vascular hemostasis by altering the production of anticoagulant factors. Recent reports of genetic mutations in the endothelial cells of patients with PH further underscore the role of these cells
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