{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T19:15:50Z","timestamp":1782587750728,"version":"3.54.5"},"reference-count":54,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2014,8,15]]},"abstract":"\n Background<\/jats:title>\n \n Right ventricular (\n RV<\/jats:styled-content>\n ) failure is a major cause of mortality worldwide and is often a consequence of\n RV<\/jats:styled-content>\n pressure overload (\n RVPO<\/jats:styled-content>\n ). Endoglin is a coreceptor for the profibrogenic cytokine, transforming growth factor beta 1 (\n TGF<\/jats:styled-content>\n \u2010\u03b21).\n TGF<\/jats:styled-content>\n \u2010\u03b21 signaling by the canonical transient receptor protein channel 6 (\n TRPC<\/jats:styled-content>\n \u20106) was recently reported to stimulate calcineurin\u2010mediated myofibroblast transformation, a critical component of cardiac fibrosis. We hypothesized that reduced activity of the\n TGF<\/jats:styled-content>\n \u2010\u03b21 coreceptor, endoglin, limits\n RV<\/jats:styled-content>\n calcineurin expression and improves survival in\n RVPO<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n We first demonstrate that endoglin is required for\n TGF<\/jats:styled-content>\n \u2010\u03b21\u2010mediated calcineurin\/\n TRPC<\/jats:styled-content>\n \u20106 expression and up\u2010regulation of alpha\u2010smooth muscle antigen (\u03b1\u2010\n SMA<\/jats:styled-content>\n ), a marker of myofibroblast transformation, in human\n RV<\/jats:styled-content>\n fibroblasts. Using endoglin haploinsufficient mice (Eng\n +\/\u2212<\/jats:sup>\n ) we show that reduced endoglin activity preserves\n RV<\/jats:styled-content>\n function, limits\n RV<\/jats:styled-content>\n fibrosis, and attenuates activation of the calcineurin\/\n TRPC<\/jats:styled-content>\n \u20106\/\u03b1\u2010\n SMA<\/jats:styled-content>\n pathway in a model of angio\u2010obliterative pulmonary hypertension. Next, using Eng\n +\/\u2212<\/jats:sup>\n mice or a neutralizing antibody (Ab) against endoglin (N\u2010Eng) in wild\u2010type mice, we show that reduced endoglin activity improves survival and attenuates\n RV<\/jats:styled-content>\n fibrosis in models of\n RVPO<\/jats:styled-content>\n induced by pulmonary artery constriction. To explore the utility of targeting endoglin, we observed a reversal of\n RV<\/jats:styled-content>\n fibrosis and calcineurin levels in wild\u2010type mice treated with a N\u2010Eng Ab, compared to an immunoglobulin G control.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n These data establish endoglin as a regulator of\n TGF<\/jats:styled-content>\n \u2010\u03b21 signaling by calcineurin and\n TRPC<\/jats:styled-content>\n \u20106 in the\n RV<\/jats:styled-content>\n and identify it as a potential therapeutic target to limit\n RV<\/jats:styled-content>\n fibrosis and improve survival in\n RVPO<\/jats:styled-content>\n , a common cause of death in cardiac and pulmonary disease.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.114.000965","type":"journal-article","created":{"date-parts":[[2014,7,12]],"date-time":"2014-07-12T03:19:09Z","timestamp":1405135149000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":30,"title":["Reducing Endoglin Activity Limits Calcineurin and TRPC\u20106 Expression and Improves Survival in a Mouse Model of Right Ventricular Pressure Overload"],"prefix":"10.1161","volume":"3","author":[{"given":"Navin K.","family":"Kapur","sequence":"first","affiliation":[{"name":"The Molecular Cardiology Research Institute and Surgical Research Laboratories, Tufts Medical Center and Tufts University School of Medicine, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Qiao","sequence":"additional","affiliation":[{"name":"The Molecular Cardiology Research Institute and Surgical Research Laboratories, Tufts Medical Center and Tufts University School of Medicine, 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MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kishan","family":"Ughreja","sequence":"additional","affiliation":[{"name":"The Molecular Cardiology Research Institute and Surgical Research Laboratories, Tufts Medical Center and Tufts University School of Medicine, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J.","family":"Morine","sequence":"additional","affiliation":[{"name":"The Molecular Cardiology Research Institute and Surgical Research Laboratories, Tufts Medical Center and Tufts University School of Medicine, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Levine","sequence":"additional","affiliation":[{"name":"The Molecular Cardiology Research Institute and Surgical Research Laboratories, Tufts Medical Center and Tufts University School of Medicine, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Aronovitz","sequence":"additional","affiliation":[{"name":"The Molecular Cardiology Research Institute and Surgical Research Laboratories, Tufts Medical Center and Tufts University School of Medicine, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas S.","family":"Hill","sequence":"additional","affiliation":[{"name":"The Molecular Cardiology Research Institute and Surgical Research Laboratories, Tufts Medical Center and Tufts University School of Medicine, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris Z.","family":"Jaffe","sequence":"additional","affiliation":[{"name":"The Molecular Cardiology Research Institute and Surgical Research Laboratories, Tufts Medical Center and Tufts University School of Medicine, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Letarte","sequence":"additional","affiliation":[{"name":"Molecular Structure and Function Program, 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