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We hypothesized that improving vagal activity could attenuate cardiac fibrosis induced by angiotensin II (Ang II) <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic>. Rats were subjected to abdominal aorta constriction (AAC) with or without pyridostigmine (PYR) (31\u2009mg\/kg\/d). After 8 weeks, PYR significantly decreased Ang II level, AT1 protein expression and collagen deposition in cardiac tissue and improved heart rate variability, baroreflex sensitivity and cardiac function, which were abolished by atropine. <jats:italic>In vitro<\/jats:italic>, treatment of cardiac fibroblasts (CFs) with Ang II (10<jats:sup>\u22127<\/jats:sup>\u2009M) increased cell proliferation, migration, transformation and secretory properties, which were significantly diminished by acetylcholine (ACh, 10<jats:sup>\u22126<\/jats:sup>\u2009M). Subsequently, Ang II significantly increased collagen type I expression as well as metalloproteinase (MMP)-2 expression and activity. Transforming growth factor (TGF)-\u03b21 expression and Smad3 phosphorylation presented a similar trend. Notably, the knockdown of the acetylcholine M<jats:sub>2<\/jats:sub> receptor by siRNA could abolish ACh anti-fibrotic action. These data implicated cholinesterase inhibitor can increase vagal activity and reduce local Ang II level and ACh inhibit Ang II pro-fibrotic effects. Our findings suggested that the parasympathetic nervous system can serve as a promising target for cardiac remodeling treatment.<\/jats:p>","DOI":"10.1038\/srep17108","type":"journal-article","created":{"date-parts":[[2015,11,24]],"date-time":"2015-11-24T10:15:35Z","timestamp":1448360135000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Improving vagal activity ameliorates cardiac fibrosis induced by angiotensin II: in vivo and in vitro"],"prefix":"10.1038","volume":"5","author":[{"given":"Jin-Jun","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Jiang","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-hua","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Jin","family":"Zang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2015,11,24]]},"reference":[{"key":"BFsrep17108_CR1","doi-asserted-by":"publisher","first-page":"C82","DOI":"10.1152\/ajpcell.00287.2006","volume":"292","author":"PK Mehta","year":"2007","unstructured":"Mehta, P. 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