title: Syndecan-4 prevents cardiac rupture and dysfunction after myocardial infarction.
abstract: BACKGROUND
  Syndecan-4 (Syn4), a cell-surface heparan sulfate proteoglycan, has been detected in the infarct region after myocardial infarction (MI), but its functional significance has not been elucidated.
  
  
  OBJECTIVE
  We examined whether and how Syn4 regulates the cardiac healing process after MI.
  
  
  RESULTS
  Although the heart in Syn4-deficient (Syn4(-/-)) mice was morphologically and functionally normal, Syn4(-/-) mice exhibited impaired heart function and increased mortality rate as a result of cardiac ruptures after MI. Cardiac ruptures in Syn4(-/-) mice were associated with reduced inflammatory reaction and impaired granulation tissue formation during the early phase of MI, as evidenced by reduced numbers of leukocytes, fibroblasts, myofibroblasts, macrophages, and capillary vessels, along with reduced extracellular matrix protein deposition in the infarct region after MI. Transforming growth factor-β1-dependent cell signaling was preserved, whereas cell migration, fibronectin-induced cell signaling, and differentiation into myofibroblasts were defective in Syn4(-/-) cardiac fibroblasts. We also found that Syn4 was involved in basic fibroblast growth factor-dependent endothelial cell signaling, cell proliferation, and tube formation. Finally, overexpression of the shed form of Syn4 before MI creation led to an increase in mortality due to cardiac rupture via its action as a dominant-negative inhibitor of endogenous Syn4 signaling, which suggested a protective role of Syn4 signaling in MI.
  
  
  CONCLUSIONS
  These results suggest that Syn4 plays an important role in the inflammatory response and granulation tissue formation, thereby preventing cardiac rupture and dysfunction after MI.
authors.affiliation: Department of Matrix Medicine, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan. matsui@igm.hokudai.ac.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Matsui
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ikesue
authors.forename: Keiko
authors.initials: K
authors.lastname: Danzaki
authors.forename: Junko
authors.initials: J
authors.lastname: Morimoto
authors.forename: Mami
authors.initials: M
authors.lastname: Sato
authors.forename: Shinya
authors.initials: S
authors.lastname: Tanaka
authors.forename: Tetsuhito
authors.initials: T
authors.lastname: Kojima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsutsui
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Uede
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D009205:Myocarditis / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D010447:Peptide Hydrolases / Q000235:genetics; D020127:Recovery of Function / Q000502:physiology; D012422:Rupture, Spontaneous; D053671:Syndecan-4 / Q000235:genetics* / Q000378:metabolism*; D014463:Ultrasonography; D015854:Up-Regulation / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology*; D014945:Wound Healing / Q000502:physiology
chemical_list: D018925:Chemokines; D016207:Cytokines; D016326:Extracellular Matrix Proteins; C508306:Sdc4 protein, mouse; D053671:Syndecan-4; D016222:Fibroblast Growth Factor 2; D010447:Peptide Hydrolases