doi: 10.1161/01.CIR.0000132476.87231.6F
(Circulation. 2004;109:2947-2952.)
© 2004 American Heart Association, Inc.
Special Reviews |
Pulmonary Arterial Hypertension
Future Directions: Report of a National Heart, Lung and Blood Institute/Office of Rare Diseases Workshop*
From the Departments of Medicine, Nashville VA Medical Center (GRECC), and Vanderbilt University, Nashville, Tenn (J.H.N., J.E.L.); Department of Medicine, New England Medical Center, Boston, Mass (B.L.F.); Division of Cardiology, University of Alberta Hospital, Edmonton, Alberta, Canada (S.L.A.); Department of Medicine, University of Colorado Health Science Center, Denver, Colo (D.B.B., D.M.R., N.F.V.); Pulmonary Hypertension Center (R.J.B.) and Department of Medicine (J.A.K., J.M.), Columbia University and College of Physicians and Surgeons, New York, NY; Departments of Medicine and Pathology, Johns Hopkins University School of Medicine, Baltimore, Md (J.G.N.G., R.M.T.); Departments of Medicine/Pulmonary and Critical Care and Pediatrics, Stanford University Medical Center, Stanford, Calif ( P.N.K., M.R.); Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minn (M.D.M.); Division and Program in Human Genetics, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio (W.C.N.); Department of Pharmacology, Center for Lung Biology, University of South Alabama, College of Medicine, Mobile (T.S.); and Division of Lung Diseases, NHLBI, Bethesda, Md (D.B.G.).
Correspondence to Dorothy B. Gail, PhD, Director, Lung Biology and Disease Program Division of Lung Diseases, NHLBI, 6701 Rockledge Dr, Suite 10018 Bethesda, MD 20892-7952. E-mail gaild@nhlbi.nih.gov
Key Words: circulation • hypertension, pulmonary • pulmonary heart disease • vasculature
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Pulmonary arterial hypertension (PAH) is characterized by vascular obstruction and the variable presence of vasoconstriction, leading to increased pulmonary vascular resistance and right-sided heart failure. PAH can present in an idiopathic form, usually called primary pulmonary hypertension (PPH), and PAH is also associated with the scleroderma spectrum of diseases, HIV infection, portal hypertension with or without cirrhosis, and anorectic drug ingestion. Idiopathic PAH occurs in women more often than men (>2:1), has a mean age at diagnosis of 36 years, and is usually fatal within 3 years if untreated. Modern treatment has markedly improved physical function and has extended survival, and the 5-year mortality rate is 
50%. We still do not understand what initiates the disease or what allows it to progress. New studies of the pathogenetic basis of PAH will lead to targeted therapies for PAH. The National Heart, Lung and Blood Institute (NHLBI) and the Office of Rare Diseases (ORD), National Institutes of Health, convened a workshop to bring together investigators with various interests in vascular biology and pulmonary hypertension to identify new research directions. Discussion included genetics of PAH, receptor function, mediators, ion channels, extracellular matrix, signaling, and potential clinical approaches.
Background and Questions
Molecular genetic studies have demonstrated mutations in a receptor in the transforming growth factor (TGF-ß) superfamily, called bone morphogenetic protein receptor 2 (BMPR2), in most cases of familial pulmonary hypertension.1,2 Less common mutations associated with PAH occur in Alk1, a TGF receptor that also causes hereditary hemorrhagic telangectasia.3 Because only 10% to 20% of persons with
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