title: Increased expression of syndecan-1 protects against cardiac dilatation and dysfunction after myocardial infarction.
abstract: BACKGROUND
  The cell-associated proteoglycan syndecan-1 (Synd1) closely regulates inflammation and cell-matrix interactions during wound healing and tumorigenesis. The present study investigated whether Synd1 may also regulate cardiac inflammation, matrix remodeling, and function after myocardial infarction (MI).
  
  
  RESULTS
  First, we showed increased protein and mRNA expression of Synd1 from 24 hours on, reaching its maximum at 7 days after MI and declining thereafter. Targeted deletion of Synd1 resulted in increased inflammation and accelerated, yet functionally adverse, infarct healing after MI. In concordance, adenoviral gene expression of Synd1 protected against exaggerated inflammation after MI, mainly by reducing transendothelial adhesion and migration of leukocytes, as shown in vitro. Increased inflammation in the absence of Synd1 resulted in increased monocyte chemoattractant protein-1 expression, increased activity of matrix metalloproteinase-2 and -9, and decreased activity of tissue transglutaminase, associated with increased collagen fragmentation and disorganization. Exaggerated inflammation and adverse matrix remodeling in the absence of Synd1 increased cardiac dilatation and impaired systolic function, whereas gene overexpression of Synd1 reduced inflammation and protected against cardiac dilatation and failure.
  
  
  CONCLUSIONS
  Increased expression of Synd1 in the infarct protects against exaggerated inflammation and adverse infarct healing, thereby reducing cardiac dilatation and dysfunction after MI in mice.
authors.affiliation: Experimental and Molecular Cardiology/CARIM, University Hospital Maastricht, PO Box 5800, 6202 AZ Maastricht, The Netherlands.
authors.forename: Davy
authors.initials: D
authors.lastname: Vanhoutte
authors.forename: Mark W M
authors.initials: MW
authors.lastname: Schellings
authors.forename: Martin
authors.initials: M
authors.lastname: Götte
authors.forename: Melissa
authors.initials: M
authors.lastname: Swinnen
authors.forename: Veronica
authors.initials: V
authors.lastname: Herias
authors.forename: Martin K
authors.initials: MK
authors.lastname: Wild
authors.forename: Dietmar
authors.initials: D
authors.lastname: Vestweber
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Chorianopoulos
authors.forename: Víctor
authors.initials: V
authors.lastname: Cortés
authors.forename: Attilio
authors.initials: A
authors.lastname: Rigotti
authors.forename: Mary-Ann
authors.initials: MA
authors.lastname: Stepp
authors.forename: Frans
authors.initials: F
authors.lastname: Van de Werf
authors.forename: Peter
authors.initials: P
authors.lastname: Carmeliet
authors.forename: Yigal M
authors.initials: YM
authors.lastname: Pinto
authors.forename: Stephane
authors.initials: S
authors.lastname: Heymans
mesh_terms: D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D003094:Collagen / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006321:Heart / Q000502:physiology; D007962:Leukocytes / Q000276:immunology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016296:Mutagenesis; D009203:Myocardial Infarction / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D053668:Syndecan-1 / Q000235:genetics* / Q000502:physiology*; D013599:Systole / Q000235:genetics; D020257:Ventricular Remodeling / Q000235:genetics* / Q000276:immunology
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D003094:Collagen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9