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The aim of this study was to determine the effects of PFD on MI-induced cardiac fibrosis and the possible underlying mechanisms in rats. After establishment of the model, animals were administered PFD by gavage for 4 weeks. During the development of MI-induced cardiac fibrosis, we found activation of a positive feedback loop between the angiotensin II type 1 receptor (AT1R)\/phospho-p38 mitogen-activated protein kinase (p38 MAPK) pathway and renin-angiotensin system (RAS), which was accompanied by down-regulation of liver X receptor-\u03b1 (LXR-\u03b1) expression. PFD attenuated body weight, heart weight, left ventricular weight, left ventricular systolic pressure, and \u00b1dp\/dt<jats:sub>max<\/jats:sub> changes induced by MI, which were associated with a reduction in cardiac fibrosis, infarct size, and hydroxyproline concentration. Moreover, PFD inhibited the AT1R\/p38 MAPK pathway, corrected the RAS imbalance [decreased angiotensin-converting enzyme (ACE), angiotensin II, and angiotensin II type 1 receptor expression, but increased ACE2 and angiotensin (1-7) activity and Mas expression] and strongly enhanced heart LXR-\u03b1 expression. These results indicate that the cardioprotective effects of PFD may be due, in large part, to controlling the feedback loop of the AT1R\/p38 MAPK\/RAS axis by activation of LXR-\u03b1.<\/jats:p>","DOI":"10.1038\/srep40523","type":"journal-article","created":{"date-parts":[[2017,1,16]],"date-time":"2017-01-16T10:49:13Z","timestamp":1484563753000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Pirfenidone controls the feedback loop of the AT1R\/p38 MAPK\/renin-angiotensin system axis by regulating liver X receptor-\u03b1 in myocardial infarction-induced cardiac fibrosis"],"prefix":"10.1038","volume":"7","author":[{"given":"Chunmei","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonglin","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanshen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwei","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,1,16]]},"reference":[{"key":"BFsrep40523_CR1","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/j.yjmcc.2014.12.007","volume":"79","author":"N Li","year":"2015","unstructured":"Li, N. et al. 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