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There is now accumulating evidence that the renin\u2010angiotensin\u2010aldosterone system is activated and contributes to cardiopulmonary remodeling that occurs in PAH. Increased plasma and lung tissue levels of angiotensin and aldosterone have been detected in experimental models of PAH and shown to correlate with cardiopulmonary hemodynamics and pulmonary vascular remodeling. These processes are abrogated by treatment with angiotensin receptor or mineralocorticoid receptor antagonists. At a cellular level, angiotensin and aldosterone activate oxidant stress signaling pathways that decrease levels of bioavailable nitric oxide, increase inflammation, and promote cell proliferation, migration, extracellular matrix remodeling, and fibrosis. Clinically, enhanced renin\u2010angiotensin activity and elevated levels of aldosterone have been detected in patients with PAH, which suggests a role for angiotensin and mineralocorticoid receptor antagonists in the treatment of PAH. This review will examine the current evidence linking renin\u2010angiotensin\u2010aldosterone system activation to PAH with an emphasis on the cellular and molecular mechanisms that are modulated by aldosterone and may be of importance for the pathobiology of PAH.<\/jats:p>","DOI":"10.1086\/675984","type":"journal-article","created":{"date-parts":[[2014,5,16]],"date-time":"2014-05-16T15:20:12Z","timestamp":1400253612000},"page":"200-210","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":112,"title":["The Role of the Renin\u2010Angiotensin\u2010Aldosterone System in the Pathobiology of Pulmonary Arterial Hypertension (2013 Grover Conference Series)"],"prefix":"10.1002","volume":"4","author":[{"given":"Bradley A.","family":"Maron","sequence":"first","affiliation":[{"name":"Brigham and Women's Hospital Division of Cardiovascular Medicine Boston Massachusetts USA"},{"name":"Veterans Affairs Boston Healthcare System 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