{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:34:45Z","timestamp":1790948085562,"version":"4.1.0"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:sec>\n            <jats:title>BACKGROUND:<\/jats:title>\n            <jats:p>Excess aldosterone is implicated in vascular calcification (VC), but the mechanism by which aldosterone-MR (mineralocorticoid receptor) complex promotes VC is unclear. Emerging evidence indicates that long-noncoding RNA H19 (H19) plays a critical role in VC. We examined whether aldosterone-induced osteogenic differentiation of vascular smooth muscle cells (VSMCs) through H19 epigenetic modification of Runx2 (runt-related transcription factor-2) in a MR-dependent manner.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>METHODS:<\/jats:title>\n            <jats:p>We induced in vivo rat model of chronic kidney disease using a high adenine and phosphate diet to explore the relationship among aldosterone, MR, H19, and VC. We also cultured human aortic VSMCs to explore the roles of H19 in aldosterone-MR complex\u2013induced osteogenic differentiation and calcification of VSMCs.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>RESULTS:<\/jats:title>\n            <jats:p>H19 and Runx2 were significantly increased in aldosterone-induced VSMC osteogenic differentiation and VC, both in vitro and in vivo, which were significantly blocked by the MR antagonist spironolactone. Mechanistically, our findings reveal that the aldosterone-activated MR bound to H19 promoter and increased its transcriptional activity, as determined by chromatin immunoprecipitation, electrophoretic mobility shift assay, and luciferase reporter assay. Silencing H19 increased microRNA-106a-5p (miR-106a-5p) expression, which subsequently inhibited aldosterone-induced Runx2 expression at the posttranscriptional level. Importantly, we observed a direct interaction between H19 and miR-106a-5p, and downregulation of miR-106a-5p efficiently reversed the suppression of Runx2 induced by H19 silencing.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>CONCLUSIONS:<\/jats:title>\n            <jats:p>Our study clarifies a novel mechanism by which upregulation of H19 contributes to aldosterone-MR complex-promoted Runx2-dependent VSMC osteogenic differentiation and VC through sponging miR-106a-5p. These findings highlight a potential therapeutic target for aldosterone-induced VC.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.123.319308","type":"journal-article","created":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T09:00:22Z","timestamp":1688634022000},"page":"1684-1699","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":21,"title":["Upregulated LncRNA H19 Sponges MiR-106a-5p and Contributes to Aldosterone-Induced Vascular Calcification via Activating the Runx2-Dependent Pathway"],"prefix":"10.1161","volume":"43","author":[{"given":"Xiong-Zhi","family":"Li","sequence":"first","affiliation":[{"name":"Department of Cardiology, Guangzhou Key Laboratory on the Molecular Mechanisms of Major Cardiovascular Disease, Guangdong Provincial Key Laboratory of Arrhythmia and Electrophysiology (X.-Z.L., Z.-C.X., Q.-Y.H., H.-F.Z., J.-F.W., J.-W.G., P.-M.L.), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China."},{"name":"Now with Cardiovascular Department, the First Affiliated Hospital of Shaoyang University, Hunan, China (X.-Z.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo-Chao","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guangzhou Key Laboratory on the Molecular Mechanisms of Major Cardiovascular Disease, Guangdong Provincial Key Laboratory of Arrhythmia and Electrophysiology (X.-Z.L., Z.-C.X., Q.-Y.H., H.-F.Z., J.-F.W., J.-W.G., P.-M.L.), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao-Ling","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology (S.-L.Z.), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-Yun","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guangzhou Key Laboratory on the Molecular Mechanisms of Major Cardiovascular Disease, Guangdong Provincial Key Laboratory of Arrhythmia and Electrophysiology (X.-Z.L., Z.-C.X., Q.-Y.H., H.-F.Z., J.-F.W., J.-W.G., P.-M.L.), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao-Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Medical Research Center (Z.-Y.L.), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9670-2642","authenticated-orcid":true,"given":"Hai-Feng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guangzhou Key Laboratory on the Molecular Mechanisms of Major Cardiovascular Disease, Guangdong Provincial Key Laboratory of Arrhythmia and Electrophysiology (X.-Z.L., Z.-C.X., Q.-Y.H., H.-F.Z., J.-F.W., J.-W.G., P.-M.L.), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Feng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guangzhou Key Laboratory on the Molecular Mechanisms of Major Cardiovascular Disease, Guangdong Provincial Key Laboratory of Arrhythmia and Electrophysiology (X.-Z.L., Z.-C.X., Q.-Y.H., H.-F.Z., J.-F.W., J.-W.G., P.-M.L.), Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Wei","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Guangzhou Key Laboratory on the Molecular Mechanisms of Major Cardiovascular Disease, Guangdong Provincial Key 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