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Increasing recognition of the importance of remodeling to the pathogenesis of PPH suggests new therapeutic possibilities, but it will be necessary to (1) identify essential mediators of remodeling, and (2) demonstrate that inhibiting those mediators suppresses remodeling before new antiremodeling therapies can be considered feasible. The effect of angiotensin-converting enzyme (ACE) inhibition on pulmonary vascular remodeling was studied in a newly developed rat model in which neointimal lesions develop between 3 and 5 wk after monocrotaline injury is coupled with increased pulmonary artery blood flow after contralateral pneumonectomy. Neointimal formation was significantly suppressed at 5 wk by ACE inhibition whether it was started 10 d before or 3 wk after remodeling was initiated, although medial hypertrophy and adventitial thickening still developed. By 11 wk, the extent of neointimal formation in rats treated with ACE inhibition was similar to rats without ACE inhibition at 5 wk. Pulmonary artery pressures and right ventricular weights correlated with the extent of neointimal formation. Northern blot analysis and in situ hybridization demonstrated marked suppression of lung tropoelastin and type I procollagen gene expression in the presence of ACE inhibition. An angiotensin II type I receptor antagonist partially, but not completely, replicated the effects of ACE inhibition. These data suggest that the tissue angiotensin system may be a target for therapeutic efforts to suppress the vascular remodeling that is characteristic of primary pulmonary hypertension.<\/jats:p>","DOI":"10.1164\/ajrccm.158.3.9710007","type":"journal-article","created":{"date-parts":[[2013,4,4]],"date-time":"2013-04-04T13:45:28Z","timestamp":1365083128000},"page":"939-950","source":"Crossref","is-referenced-by-count":49,"title":["Angiotensin-converting Enzyme Inhibition Delays Pulmonary Vascular Neointimal Formation"],"prefix":"10.1093","volume":"158","author":[{"given":"KAZUSHIGE","family":"OKADA","sequence":"first","affiliation":[{"name":"Respiratory and Critical Care Division, Washington University Medical Center, St. Louis, Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MATTHEW L.","family":"BERNSTEIN","sequence":"additional","affiliation":[{"name":"Respiratory and Critical Care Division, Washington University Medical Center, St. Louis, Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"WEI","family":"ZHANG","sequence":"additional","affiliation":[{"name":"Respiratory and Critical Care Division, Washington University Medical Center, St. Louis, Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"DANIEL P.","family":"SCHUSTER","sequence":"additional","affiliation":[{"name":"Respiratory and Critical Care Division, Washington University Medical Center, St. Louis, Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"MITCHELL D.","family":"BOTNEY","sequence":"additional","affiliation":[{"name":"Respiratory and Critical Care Division, Washington University Medical Center, St. Louis, Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[1998,9,1]]},"reference":[{"key":"2026032709084265500_B1","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1161\/01.CIR.18.4.533","article-title":"The pathology of hypertensive pulmonary vascular disease: a description of six grades of structural changes in the pulmonary arteries with special reference to congeital cardiac septal defects.","volume":"18","author":"Heath","year":"1958","journal-title":"Circulation"},{"key":"2026032709084265500_B2","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1161\/01.CIR.42.6.1163","article-title":"Primary pulmonary hypertension: a pathologic study of the lung vessels in 156 clinically diagnosed cases.","volume":"42","author":"Wagenvoort","year":"1970","journal-title":"Circulation"},{"key":"2026032709084265500_B3","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/S0025-6196(12)65277-X","article-title":"Primary pulmonary hypertension: a histopathologic study of 80 cases.","volume":"60","author":"Bjornsson","year":"1985","journal-title":"Mayo Clin. 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