{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T18:06:43Z","timestamp":1769105203284,"version":"3.49.0"},"reference-count":63,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,8,6]]},"abstract":"\n Background<\/jats:title>\n \n Ischemia\/reperfusion (I\/R) injury is a critical issue in the development of treatment strategies for ischemic heart disease. MURC (muscle\u2010restricted coiled\u2010coil protein)\/Cavin\u20104 (caveolae\u2010associated protein 4), which is a component of caveolae, is involved in the pathophysiology of dilated cardiomyopathy and cardiac hypertrophy. However, the role of\n MURC<\/jats:styled-content>\n in cardiac I\/R injury remains unknown.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n The systems network genomic analysis based on\n PC<\/jats:styled-content>\n \u2010corr network inference on microarray data between wild\u2010type and\n MURC<\/jats:styled-content>\n knockout mouse hearts predicted a network of discriminating genes associated with reactive oxygen species. To demonstrate the prediction, we analyzed I\/R\u2010injured mouse hearts.\n MURC<\/jats:styled-content>\n deletion decreased infarct size and preserved heart contraction with reactive oxygen species\u2013related molecule\n EGR<\/jats:styled-content>\n 1 (early growth response protein 1) and\n DDIT<\/jats:styled-content>\n 4 (DNA\u2010damage\u2010inducible transcript 4) suppression in I\/R\u2010injured hearts. Because\n PC<\/jats:styled-content>\n \u2010corr network inference integrated with a protein\u2013protein interaction network prediction also showed that\n MURC<\/jats:styled-content>\n is involved in the apoptotic pathway, we confirmed the upregulation of\n STAT<\/jats:styled-content>\n 3 (signal transducer and activator of transcription 3) and\n BCL<\/jats:styled-content>\n 2 (B\u2010cell lymphoma 2) and the inactivation of caspase 3 in I\/R\u2010injured hearts of\n MURC<\/jats:styled-content>\n knockout mice compared with those of wild\u2010type mice.\n STAT<\/jats:styled-content>\n 3 inhibitor canceled the cardioprotective effect of\n MURC<\/jats:styled-content>\n deletion in I\/R\u2010injured hearts. In cardiomyocytes exposed to hydrogen peroxide,\n MURC<\/jats:styled-content>\n overexpression promoted apoptosis and\n MURC<\/jats:styled-content>\n knockdown inhibited apoptosis.\n STAT<\/jats:styled-content>\n 3 inhibitor canceled the antiapoptotic effect of\n MURC<\/jats:styled-content>\n knockdown in cardiomyocytes.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Our findings, obtained by prediction from systems network genomic analysis followed by experimental validation, suggested that\n MURC<\/jats:styled-content>\n modulates cardiac I\/R injury through the regulation of reactive oxygen species\u2013induced cell death and\n STAT<\/jats:styled-content>\n 3\u2010meditated antiapoptosis. Functional inhibition of\n MURC<\/jats:styled-content>\n may be effective in reducing cardiac I\/R injury.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.119.012047","type":"journal-article","created":{"date-parts":[[2019,7,31]],"date-time":"2019-07-31T09:18:11Z","timestamp":1564564691000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Systems Network Genomic Analysis Reveals Cardioprotective Effect of MURC\/Cavin\u20104 Deletion Against Ischemia\/Reperfusion Injury"],"prefix":"10.1161","volume":"8","author":[{"given":"Masahiro","family":"Nishi","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takehiro","family":"Ogata","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine Graduate School of 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