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An adverse cardiac remodeling, such as hypertrophy and fibrosis, in non-infarcted area leads to uncompensated heart failure with cardiac dysfunction. We previously demonstrated that canstatin, a C-terminus fragment of type IV collagen \u03b12 chain, exerted anti-remodeling effect against isoproterenol-induced cardiac hypertrophy model rats. In the present study, we examined whether a long-term administration of recombinant canstatin exhibits a cardioprotective effect against the adverse cardiac remodeling in MI model rats. Left anterior descending artery of male Wistar rats was ligated and recombinant mouse canstatin (20\u00a0\u03bcg\/kg\/day) was intraperitoneally injected for 28\u00a0days. Long-term administration of canstatin improved survival rate and significantly inhibited left ventricular dilatation and dysfunction after MI. Canstatin significantly inhibited scar thinning in the infarcted area and significantly suppressed cardiac hypertrophy, nuclear translocation of nuclear factor of activated T-cells, interstitial fibrosis and increase of myofibroblasts in the non-infarcted area. Canstatin significantly inhibited transforming growth factor-\u03b21-induced differentiation of rat cardiac fibroblasts into myofibroblasts. The present study for the first time demonstrated that long-term administration of recombinant canstatin exerts cardioprotective effects against adverse cardiac remodeling in MI model rats.<\/jats:p>","DOI":"10.1038\/s41598-020-69736-y","type":"journal-article","created":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T10:24:33Z","timestamp":1596104673000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Long-term administration of recombinant canstatin prevents adverse cardiac remodeling after myocardial infarction"],"prefix":"10.1038","volume":"10","author":[{"given":"Akira","family":"Sugiyama","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rumi","family":"Ito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muneyoshi","family":"Okada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideyuki","family":"Yamawaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,7,30]]},"reference":[{"key":"69736_CR1","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1016\/j.ijcard.2012.10.046","volume":"168","author":"JA Finegold","year":"2013","unstructured":"Finegold, J. 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