{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T06:21:34Z","timestamp":1776406894938,"version":"3.51.2"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,11,6]]},"abstract":"\n Background<\/jats:title>\n \n Myocardial infarction (\n MI<\/jats:styled-content>\n ) is often accompanied by cardiomyocyte apoptosis, which decreases heart function and leads to an increased risk of heart failure. The aim of this study was to examine the effects of transforming growth factor\u2010\u03b2 receptor\n III<\/jats:styled-content>\n (\n TGF<\/jats:styled-content>\n \u03b2R3) on cardiomyocyte apoptosis during\n MI<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n An\n MI<\/jats:styled-content>\n mouse model was established by left anterior descending coronary artery ligation. Cell viability, apoptosis,\n TGF<\/jats:styled-content>\n \u03b2R3, and mitogen\u2010activated protein kinase signaling were assessed by methylthiazolyldiphenyl\u2010tetrazolium bromide assay, terminal deoxynucleotidyl transferase\u2010mediated dUTP nick end labeling assay, immunofluorescence, electron microscopy, and Western blotting. Our results demonstrated that\n TGF<\/jats:styled-content>\n \u03b2R3 expression in the border region of the heart was dynamically changed during\n MI<\/jats:styled-content>\n . After stimulation with H\n 2<\/jats:sub>\n O\n 2<\/jats:sub>\n ,\n TGF<\/jats:styled-content>\n \u03b2R3 overexpression in cardiomyocytes led to increased cell apoptosis and activation of p38 signaling, whereas\n TGF<\/jats:styled-content>\n \u03b2R3 knockdown had the opposite effect.\n ERK<\/jats:styled-content>\n 1\/2 and\n JNK<\/jats:styled-content>\n 1\/2 signaling was not altered by\n TGF<\/jats:styled-content>\n \u03b2R3 modulation, and p38 inhibitor (\n SB<\/jats:styled-content>\n 203580) reduced the effect of\n TGF<\/jats:styled-content>\n \u03b2R3 on apoptosis, suggesting that p38 has a nonredundant function in activating apoptosis. Consistent with the in\u00a0vitro observations, cardiac\n TGF<\/jats:styled-content>\n \u03b2R3 transgenic mice showed augmented cardiomyocyte apoptosis, enlarged infarct size, increased injury, and enhanced p38 signaling upon\n MI<\/jats:styled-content>\n . Conversely, cardiac loss of function of\n TGF<\/jats:styled-content>\n \u03b2R3 by adeno\u2010associated viral vector serotype 9\u2013TGF\u03b2R3 short hairpin RNA attenuated the effects of\n MI<\/jats:styled-content>\n in mice.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n TGF<\/jats:styled-content>\n \u03b2R3 promotes apoptosis of cardiomyocytes via a p38 pathway\u2013associated mechanism, and loss of\n TGF<\/jats:styled-content>\n \u03b2R3 reduces\n MI<\/jats:styled-content>\n injury, which suggests that\n TGF<\/jats:styled-content>\n \u03b2R3 may serve as a novel therapeutic target for\n MI<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.116.005357","type":"journal-article","created":{"date-parts":[[2017,5,31]],"date-time":"2017-05-31T00:40:18Z","timestamp":1496191218000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":17,"title":["Transforming Growth Factor\u2010\u03b2 Receptor III is a Potential Regulator of Ischemia\u2010Induced Cardiomyocyte Apoptosis"],"prefix":"10.1161","volume":"6","author":[{"given":"Fei","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen\u2010Qi","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia\u2010Yang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Di","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan\u2010Na","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia\u2010Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan\u2010Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of Biomedicine\u2010Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang\u2010Jiang","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology (the State\u2010Province Key Laboratories of 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