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However, the role of Mas\u2010related G protein\u2010coupled receptor member D (MrgD) in hypertension remains incompletely understood. In this study, we observed upregulated MrgD expression in the arterial tissues of hypertensive patients and animal models. In Sprague\u2010Dawley rats, MrgD overexpression elevated blood pressure (BP) and promoted mesenteric vascular remodeling, whereas MrgD knockdown in spontaneously hypertensive rats normalized BP and ameliorated vascular remodeling. Consistently, MrgD knockout mice exhibited resistance to angiotensin II (Ang II)\u2010induced hypertension and vascular injury. Mechanistic investigations demonstrated that MrgD facilitated vascular remodeling in vascular smooth muscle cells (VSMCs) through the voltage\u2010gated L\u2010type Ca\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    channel (Cav1.2)\u2010Ca\n                    <jats:sup>2<\/jats:sup>\n                    <jats:sup>+<\/jats:sup>\n                    \/calmodulin\u2010dependent protein kinase II\u03b3 (CaMKII\u03b3) signaling axis. Co\u2010immunoprecipitation coupled with mass spectrometry and in vitro functional assays confirmed that Ang II enhanced the interaction among MrgD, CaMKII\u03b3, and Cav1.2, thereby promoting VSMC phenotypic switch. Through artificial intelligence\u2010driven screening combined with functional validation, we identified risperidone as a small\u2010molecule inhibitor of MrgD that effectively attenuated hypertension and vascular remodeling. These findings established MrgD as a key contributor to the pathogenesis of hypertension and underscore its potential as a promising therapeutic target for hypertension and its associated vascular complications.\n                  <\/jats:p>","DOI":"10.1002\/mco2.70706","type":"journal-article","created":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T06:42:39Z","timestamp":1774766559000},"source":"Crossref","is-referenced-by-count":0,"title":["Mas\u2010Related G Protein\u2010Coupled Receptor Member D Sustains Hypertension"],"prefix":"10.1002","volume":"7","author":[{"given":"Kun","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Cardiology The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongxu","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of Cardiology The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukang","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Cardiology The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoguang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Cardiology The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Cardiology The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shidong","family":"Song","sequence":"additional","affiliation":[{"name":"Duofortunatherapeutic Suzhou Co. 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Suzhou Jiangsu Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery The Second Affiliated Hospital of Soochow University  Suzhou Jiangsu Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangxiang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology The First Affiliated Hospital of Nanjing Medical University  Nanjing Jiangsu Province China"},{"name":"Department of Cardiology Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital  Fuzhou, Fujian Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,28]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/jhh.2012.53"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-021-00559-8"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/hpaa195"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.303587"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01430-7"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.107.148338"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.110.149815"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20140329"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.112.268029"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.113.301077"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173384"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.312581"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg583"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.24.6.739"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.26.6.1060"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.31.5.1125"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000131495.93500.3c"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2007598117"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.71.110601.135410"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.113.01508"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1161\/hy0202.103823"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2023.1130312"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-023-01168-3"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038618"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2021.e08440"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2117435119"},{"key":"e_1_2_12_28_1","first-page":"414","article-title":"[Arterial Hypertension]","volume":"147","author":"Hengel F. 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