{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,20]],"date-time":"2025-12-20T22:11:45Z","timestamp":1766268705621,"version":"3.41.2"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,9,14]],"date-time":"2017-09-14T00:00:00Z","timestamp":1505347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["8110016781100159"],"award-info":[{"award-number":["8110016781100159"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LY15H020003"],"award-info":[{"award-number":["LY15H020003"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiovascular Therapeutics"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>We previously demonstrated that anoxia\u2010mediated Ca<jats:sup>2+<\/jats:sup> handling dysfunction could be ameliorated through inhibition of mevalonate pathway via RhoA\u2010 and Ras\u2010related mechanisms in H9c2 cells. In this study, we further explored whether inhibition of mevalonate pathway is associated with cardiac remodeling and dysfunction in ischemic cardiomyopathy, and discussed the possible role of Ras, Rac and RhoA in cardiac dysfunction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated the role of mevalonate pathway in cardiac remodeling and cardiomyocyte Ca<jats:sup>2+<\/jats:sup> handling proteins expression in a rat model of cardiac dysfunction due to myocardial infarction (<jats:styled-content style=\"fixed-case\">MI<\/jats:styled-content>). After <jats:styled-content style=\"fixed-case\">MI<\/jats:styled-content>, adult male Sprague\u2010Dawley rats were treated with drugs that antagonize key components in mevalonate pathway, including 3\u2010hydroxy\u20103\u2010methylglutaryl\u2010CoA reductase, farnesyl pyrophosphate synthase, and Rho\u2010kinase for 10\u00a0weeks. The protein expression of ryanodine receptor 2 (RyR2), sarcoplasmic reticulum Ca<jats:sup>2+<\/jats:sup> <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content>ase (<jats:styled-content style=\"fixed-case\">SERCA<\/jats:styled-content>) 2a, phospholamban (<jats:styled-content style=\"fixed-case\">PLB<\/jats:styled-content>), phospho\u2010<jats:styled-content style=\"fixed-case\">PLB<\/jats:styled-content> at serine\u201016 (<jats:styled-content style=\"fixed-case\">PS<\/jats:styled-content>er16\u2010<jats:styled-content style=\"fixed-case\">PLB<\/jats:styled-content>), <jats:styled-content style=\"fixed-case\">FKBP<\/jats:styled-content>12.6, and RhoA as well as RyR2 and <jats:styled-content style=\"fixed-case\">FKBP<\/jats:styled-content>12.6 <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> levels was evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Rosuvastatin and alendronate treatment prevented myocardial remodeling, improved cardiac function and reduced infarct size. Furthermore, rosuvastatin and alendronate promoted an increase in the protein expression of <jats:styled-content style=\"fixed-case\">SERCA<\/jats:styled-content>2a and <jats:styled-content style=\"fixed-case\">PS<\/jats:styled-content>er16\u2010<jats:styled-content style=\"fixed-case\">PLB<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">PLB<\/jats:styled-content> ratio as well as partially restored the RyR2 and <jats:styled-content style=\"fixed-case\">FKBP<\/jats:styled-content>12.6 gene and protein expression. Fasudil failed to exert these beneficial effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings indicate that mevalonate pathway inhibition by rosuvastatin and alendronate prevents cardiac remodeling and dysfunction possibly through RhoA\u2010independent mechanisms.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1755-5922.12285","type":"journal-article","created":{"date-parts":[[2017,6,30]],"date-time":"2017-06-30T15:02:06Z","timestamp":1498834926000},"source":"Crossref","is-referenced-by-count":16,"title":["Inhibition of mevalonate pathway prevents ischemia\u2010induced cardiac dysfunction in rats via RhoA\u2010independent signaling pathway"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1822-9546","authenticated-orcid":false,"given":"Ying","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Cardiology Sir Run Run Shaw Hospital College of Medicine Zhejiang University  Hangzhou 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