title: Syndecan-4 deficiency accelerates the transition from compensated hypertrophy to heart failure following pressure overload.
abstract: Increasing evidence suggests that a mismatch between angiogenesis and myocardial growth contributes to the transition from adaptive cardiac hypertrophy to heart failure following pressure overload. Syndecan-4 is a transmembrane proteoglycan that binds to growth factors and extracellular matrix proteins and is critical in focal adhesion formation. However, its effects on coronary angiogenesis during pressure overload-induced heart failure have not been studied. Here, we hypothesize that syndecan-4 modulates cardiac remodeling in response to pressure overload through its ability to regulate adaptive angiogenesis. Syndecan-4 knockout (syndecan-4 KO) and wild-type (WT) mice were subjected to pressure overload induced by transverse aortic constriction (TAC). Syndecan-4 KO mice exhibited reduced capillary density, attenuated cardiomyocyte size, and worsened left ventricular cardiac function after TAC surgery compared with WT mice. Moreover, syndecan-4 KO mice showed a significant decrease in protein kinase C alpha expression. Our data suggest that syndecan-4 is essential for the compensated hypertrophy and the maintenance of cardiac function during the process of heart failure following pressure overload.
authors.affiliation: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors.forename: Guannan
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xie
authors.affiliation: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors.forename: Jianzhou
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors.forename: Han
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors.forename: Xinlin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
authors.forename: Qinhua
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China. Electronic address: gurong.nju@163.com.
authors.forename: Rong
authors.initials: R
authors.lastname: Gu
authors.affiliation: Department of Cardiology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China. Electronic address: xubiao@medmail.com.cn.
authors.forename: Biao
authors.initials: B
authors.lastname: Xu
mesh_terms: D000818:Animals; D001011:Aorta / Q000503:physiopathology* / Q000601:surgery; D062186:Arterial Pressure; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D006333:Heart Failure / Q000209:etiology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008026:Ligation; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic; D010641:Phenotype; D051571:Protein Kinase C-alpha / Q000378:metabolism; D053671:Syndecan-4 / Q000172:deficiency* / Q000235:genetics; D013997:Time Factors; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: C508306:Sdc4 protein, mouse; D053671:Syndecan-4; C496630:Prkca protein, mouse; D051571:Protein Kinase C-alpha
keywords: Angiogenesis; Cardiac hypertrophy; Heart failure; PKCα; Syndecan-4