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Aldosterone levels are elevated in human pulmonary arterial hypertension and in experimental pulmonary hypertension, while inhibition of the aldosterone\u2010binding mineralocorticoid receptor attenuates pulmonary hypertension in multiple animal models. We explored the role of mineralocorticoid receptor in endothelial and smooth muscle cells in using cell\u2010specific mineralocorticoid receptor knockout mice exposed to sugen\/hypoxia\u2010induced pulmonary hypertension. Treatment with the mineralocorticoid receptor inhibitor spironolactone significantly reduced right ventricular systolic pressure. However, this is not reproduced by selective mineralocorticoid receptor deletion in smooth muscle cells or endothelial cells. Similarly, spironolactone attenuated the increase in right ventricular cardiomyocyte area independent of vascular mineralocorticoid receptor with no effect on right ventricular weight or interstitial fibrosis. Right ventricular perivascular fibrosis was significantly decreased by spironolactone and this was reproduced by specific deletion of mineralocorticoid receptor from endothelial cells. Endothelial cell\u2010mineralocorticoid receptor deletion attenuated the sugen\/hypoxia\u2010induced increase in the leukocyte\u2010adhesion molecule, E\u2010selectin, and collagen IIIA1\u00a0in the right ventricle. Spironolactone also significantly reduced pulmonary arteriolar muscularization, independent of endothelial cell\u2010mineralocorticoid receptor or smooth muscle cell\u2010mineralocorticoid receptor. Finally, the degree of pulmonary perivascular inflammation was attenuated by mineralocorticoid receptor antagonism and was fully reproduced by smooth muscle cell\u2010specific mineralocorticoid receptor deletion. These studies demonstrate that in the sugen\/hypoxia pulmonary hypertension model, systemic\u2010mineralocorticoid receptor blockade significantly attenuates the disease and that mineralocorticoid receptor has cell\u2010specific effects, with endothelial cell\u2010mineralocorticoid receptor contributing to right ventricular perivascular fibrosis and smooth muscle cell\u2010mineralocorticoid receptor participating in pulmonary vascular inflammation. As mineralocorticoid receptor antagonists are being investigated to treat pulmonary arterial hypertension, these findings support novel mechanisms and potential mineralocorticoid receptor targets that mediate therapeutic benefits in patients.<\/jats:p>","DOI":"10.1177\/20458940211025240","type":"journal-article","created":{"date-parts":[[2021,6,2]],"date-time":"2021-06-02T20:31:19Z","timestamp":1622665879000},"page":"1-13","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":17,"title":["Vascular cell\u2010specific roles of mineralocorticoid receptors in pulmonary hypertension"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2990-1748","authenticated-orcid":false,"given":"Divya P.","family":"Menon","sequence":"first","affiliation":[{"name":"Pulmonary, Critical Care and Sleep Division Tufts Medical Center Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanming","family":"Qi","sequence":"additional","affiliation":[{"name":"Pulmonary, Critical Care and Sleep Division Tufts Medical Center Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung K.","family":"Kim","sequence":"additional","affiliation":[{"name":"Molecular Cardiology Research Institute Tufts Medical Center Boston MA USA"},{"name":"Department of Sports Science Seoul National University of Science and Technology Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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