title: Syndecan-4 over-expression preserves cardiac function in a rat model of myocardial infarction.
abstract: Syndecan-4 (synd4) is a heparan sulfate proteoglycan, involved in repair following tissue damage, through modulating neovascularization and inflammation. In acute myocardial infarction its myocardial expression is up-regulated in a time-dependent manner, and in synd4-deficient mice severe cardiac dysfunction and abnormal remodeling are observed following induction of myocardial infarction. Here we explored the therapeutic potential of sustained synd4 over-expression in the context of myocardial infarction. Adenovirus containing the synd4 gene (Ad-synd4), or corresponding control adenovirus (Ad-null), was administered intramyocardially in rats immediately after induction of myocardial infarction. Cardiac function was ascertained by echocardiography, hemodynamic assessment and brain natriuretic peptide level 28 days post-intervention. Hearts were excised for molecular and histological analyses at predetermined time points. We observed reduced mortality and improved cardiac function post-myocardial infarction in the Ad-synd4 as compared to the Ad-null group, with associated attenuation of cardiac remodeling, less myocyte loss and reduced fibrosis. Additionally, the Ad-synd4 group exhibited endothelial cell activation and increased angiogenesis and arteriogenesis in the myocardium. The Ad-synd4 group also showed evidence of reduced myocardial inflammation as compared with the Ad-null group, with reduced inflammatory cell (CD45+) and myofibroblast (α-SMA+) infiltration as well as suppressed collagen III deposition and iNOS expression. Our results suggest that sustained synd4 over-expression in the myocardium is of therapeutic benefit following experimental myocardial infarction, through inducing neovascularization, suppressing tissue inflammation and fibrosis, with resultant improvements in cardiac function and remodeling.
authors.affiliation: Department of Cardiology, Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xie
authors.forename: Jingjing
authors.initials: J
authors.lastname: Wang
authors.forename: Ruotian
authors.initials: R
authors.lastname: Li
authors.forename: Qin
authors.initials: Q
authors.lastname: Dai
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Yong
authors.forename: Bing
authors.initials: B
authors.lastname: Zong
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Xu
authors.forename: Erguang
authors.initials: E
authors.lastname: Li
authors.forename: Albert
authors.initials: A
authors.lastname: Ferro
authors.forename: Biao
authors.initials: B
authors.lastname: Xu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053671:Syndecan-4 / Q000235:genetics / Q000378:metabolism*
chemical_list: D053671:Syndecan-4