Year: 2004
Type: article
Abstract: ulmonary 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 (Ͼ2:1), 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 Ϸ50%.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 biol-ogy 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 QuestionsMolecular genetic studies have demonstrated mutations in a receptor in the transforming growth factor (TGF-) 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 Ϸ10% to 20% of persons with a BMPR2 mutation develop PAH, it is likely that other genes, genetic polymorphisms, and environmental factors are necessary to initiate the pathological sequence that leads to disease. 4 Most cases of PAH are not associated with known inherited genetic mutations.5 Thus, external stimuli coupled with as-yet-undefined genetic susceptibility to disease are
Source: Circulation
Authors: John H. Newman, Barry L. Fanburg, Stephen L. Archer, David B. Badesch, Robyn J. Barst, Joe G.N. Garcia, Peter N. Kao, James A. Knowles, James E. Loyd, Michael D. McGoon, Jane H. Morse, William C. Nichols, Marlene Rabinovitch, David M. Rodman, Troy Stevens, Rubin M. Tuder, Norbert F. Voelkel, Dorothy B. Gail
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2169950372