{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T06:42:07Z","timestamp":1777963327059,"version":"3.51.4"},"reference-count":43,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,7,6]],"date-time":"2016-07-06T00:00:00Z","timestamp":1467763200000},"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":["NSFC, 81070088"],"award-info":[{"award-number":["NSFC, 81070088"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiovascular Therapeutics"],"published-print":{"date-parts":[[2016,8]]},"abstract":"Summary<\/jats:title>Objectives<\/jats:title>Inflammation after myocardial infarction (MI<\/jats:styled-content>) causes cardiac nerve sprouting and consequent ventricular arrhythmias (VA<\/jats:styled-content>s). Macrophages, as major immune cells, are involved in the entire inflammation response process and serve as a link between inflammation and sympathetic hyperinnervation by regulating nerve growth factor (NGF<\/jats:styled-content>) expression. Accumulating evidence shows that statins possess antiarrhythmogenic properties, and the aim of this study was to explore the mechanism by which atorvastatin ameliorates cardiac sympathetic nerve sprouting via regulating macrophage polarization.<\/jats:p><\/jats:sec>Methods<\/jats:title>Rat models of MI<\/jats:styled-content> were created by ligating the left coronary artery. MI<\/jats:styled-content>\u2010operated rats received either atorvastatin or phosphate\u2010buffered saline for 7\u00a0days. Immunohistochemical analyses and immunofluorescence staining were used to analyze macrophage infiltration after MI<\/jats:styled-content> and to detect the distribution and density of growth\u2010associated protein\u201043 (GAP<\/jats:styled-content>\u201043) and tyrosine hydroxylase (TH<\/jats:styled-content>) in nerve fibers in peri\u2010infarct zones after MI<\/jats:styled-content>. The polarity of the macrophages that were obtained from the rat peritoneal cavity was examined via flow cytometry. The protein levels of NGF<\/jats:styled-content> were detected via Western blot analysis, and the concentrations of NGF<\/jats:styled-content> in the supernatants were determined via enzyme\u2010linked immunosorbent assay. The mRNA<\/jats:styled-content> levels of NGF<\/jats:styled-content>, inducible nitric oxide synthase (iNOS<\/jats:styled-content>), Arginase\u20101 (Arg1), interleukin\u20101\u03b2 (IL<\/jats:styled-content>\u20101\u03b2), and tumor necrosis factor\u2010\u03b1 (TNF<\/jats:styled-content>\u2010\u03b1) were examined by quantitative real\u2010time polymerase chain reaction. The association between VA<\/jats:styled-content>s and MI<\/jats:styled-content> was evaluated using programmed electrophysiological stimulation.<\/jats:p><\/jats:sec>Results<\/jats:title>Macrophages were successfully induced to the M1 (classically activated) and M2 (alternatively activated) phenotypes by stimulation with lipopolysaccharide and interferon\u2010\u03b3 (LPS<\/jats:styled-content>\u00a0+\u00a0IFN<\/jats:styled-content>\u2010\u03b3) and interleukin\u20104 (IL<\/jats:styled-content>\u20104), respectively. Atorvastatin markedly downregulated IL<\/jats:styled-content>\u20101\u03b2, TNF<\/jats:styled-content>\u2010\u03b1, iNOS<\/jats:styled-content>, and NGF<\/jats:styled-content> and upregulated Arg1, shifting the macrophage phenotype from M1 to M2. Moreover, atorvastatin significantly reduced TH<\/jats:styled-content> levels and the density of GAP<\/jats:styled-content>\u201043\u2010positive nerve fibers and decreased inducible VA<\/jats:styled-content>s.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Atorvastatin effectively ameliorated cardiac sympathetic nerve remodeling and prevented VA<\/jats:styled-content>s after MI<\/jats:styled-content> by significantly downregulating the expression of NGF<\/jats:styled-content>, IL<\/jats:styled-content>\u20101\u03b2, and TNF<\/jats:styled-content>\u2010\u03b1 via together with the augmentation of M2 macrophage.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1755-5922.12193","type":"journal-article","created":{"date-parts":[[2016,5,5]],"date-time":"2016-05-05T14:31:18Z","timestamp":1462458678000},"page":"234-244","source":"Crossref","is-referenced-by-count":35,"title":["Atorvastatin attenuates sympathetic hyperinnervation together with the augmentation of M2 macrophages in rats postmyocardial 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