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Elevated levels of aldosterone activate Akt, and, in pulmonary arterial hypertension (PAH), correlate with pulmonary arteriole thickening, which suggests that mTORC1 regulation by aldosterone may mediate adverse pulmonary vascular remodeling. We hypothesized that aldosterone\u2010Raptor signaling induces abnormal pulmonary artery smooth muscle cell (PASMC) survival patterns to promote PAH. Remodeled pulmonary arterioles from SU\u20105416\/hypoxia\u2010PAH rats and monocrotaline\u2010PAH rats with hyperaldosteronism expressed increased levels of the Raptor target, p70S6K, which provided a basis for investigating aldosterone\u2010Raptor signaling in human PASMCs. Aldosterone (10\n                    <jats:sup>\u20109<\/jats:sup>\n                    to 10\n                    <jats:sup>\u20107<\/jats:sup>\n                    M) increased Akt\/mTOR\/Raptor to activate p70S6K and increase proliferation, viability, and apoptosis resistance in PASMCs. In PASMCs transfected with Raptor\u2010small interfering RNA or treated with spironolactone\/eplerenone, aldosterone or pulmonary arterial plasma from patients with PAH failed to increase p70S6K activation or to induce cell survival\n                    <jats:italic>in vitro.<\/jats:italic>\n                    Optimal inhibition of pulmonary arteriole Raptor was achieved by treatment with Staramine\u2010monomethoxy polyethylene glycol that was formulated with Raptor\u2010small interfering RNA plus spironolactone\n                    <jats:italic>in vivo<\/jats:italic>\n                    , which decreased arteriole muscularization and pulmonary hypertension in 2 experimental animal models of PAH\n                    <jats:italic>in vivo.<\/jats:italic>\n                    Up\u2010regulation of mTORC1 by aldosterone is a critical pathobiologic mechanism that controls PASMC survival to promote hypertrophic vascular remodeling and PAH.\u2014Aghamohammadzadeh, R., Zhang, Y.\u2010Y., Stephens, T. E., Arons, E., Zaman, P., Polach, K. J., Matar, M., Yung, L.\u2010M., Yu, P. B., Bowman, F. P., Opotowsky, A. R., Waxman, A. B., Loscalzo, J., Leopold, J. A., Maron, B. A. Up\u2010regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth muscle cell survival patterns to promote pulmonary arterial hypertension. FASEB J. 30, 2511\u20102527 (2016).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201500042","type":"journal-article","created":{"date-parts":[[2016,3,22]],"date-time":"2016-03-22T23:14:42Z","timestamp":1458688482000},"page":"2511-2527","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Up\u2010regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth muscle cell survival patterns to promote pulmonary arterial hypertension"],"prefix":"10.1096","volume":"30","author":[{"given":"Reza","family":"Aghamohammadzadeh","sequence":"first","affiliation":[{"name":"Department of Medicine Division of Cardiovascular Medicine Brigham and Women's Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying\u2010Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Cardiovascular Medicine Brigham and Women's Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas E.","family":"Stephens","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Cardiovascular Medicine Brigham and Women's Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Arons","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Cardiovascular Medicine Brigham and Women's Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Zaman","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Cardiovascular Medicine Brigham and Women's Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J.","family":"Polach","sequence":"additional","affiliation":[{"name":"Celsion Corporation Lawrenceville New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majed","family":"Matar","sequence":"additional","affiliation":[{"name":"Celsion Corporation Lawrenceville New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lai\u2010Ming","family":"Yung","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Cardiovascular Medicine Brigham and Women's Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul B.","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Cardiovascular Medicine Brigham and Women's Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick P.","family":"Bowman","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Cardiovascular Medicine Brigham and Women's Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander R.","family":"Opotowsky","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Cardiovascular Medicine Brigham and Women's Hospital Boston Massachusetts USA"},{"name":"Department of Cardiology Boston Children's Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron B.","family":"Waxman","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Pulmonary and Critical Care Medicine Brigham and Women's Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Loscalzo","sequence":"additional","affiliation":[{"name":"Department of Medicine Division of Cardiovascular Medicine 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