title: A collagen α2(I) mutation impairs healing after experimental myocardial infarction.
abstract: Collagen breakdown and de novo synthesis are important processes during early wound healing after myocardial infarction (MI). We tested the hypothesis that collagen I, the main constituent of the extracellular matrix, affects wound healing after MI. The osteogenesis imperfecta mouse (OIM), lacking procollagen-α2(I) expression, represents a model of the type III form of the disease in humans. Homozygous (OIM/OIM), heterozygous (OIM/WT), and wild-type (WT/WT) mice were subjected to a permanent myocardial infarction protocol or sham surgery. Baseline functional and geometrical parameters determined by echocardiography did not differ between genotypes. After MI but not after sham surgery, OIM/OIM animals exhibited significantly increased mortality, due to early ventricular rupture between day 3 and 7. Echocardiography at day 1 demonstrated increased left ventricular dilation in OIM/OIM animals. Less collagen I mRNA within the infarct area was found in OIM/OIM animals. At 2 days after MI, MMP-9 expression in the infarct border zone was higher in OIM/OIM than in WT/WT animals. Increased granulocyte infiltration into the infarct border zone occurred in OIM/OIM animals. Neither granulocyte depletion nor MMP inhibition reduced mortality in OIM/OIM animals. In this murine model, deficiency of collagen I leads to a myocardial wound-healing defect. Both structural alterations within pre-existing collagen matrix and impaired collagen de novo expression contribute to a high rate of early myocardial rupture after MI.
authors: Department of Internal Medicine I, Comprehensive Heart Failure Center, University Clinic, University of Würzburg, Würzburg, Germany. hofmann_u2@klinik.uni-wuerzburg.de
authors: Ulrich
authors: U
authors: Hofmann
authors: Andreas
authors: A
authors: Bonz
authors: Stefan
authors: S
authors: Frantz
authors: Kai
authors: K
authors: Hu
authors: Christiane
authors: C
authors: Waller
authors: Katrin
authors: K
authors: Roemer
authors: Jürgen
authors: J
authors: Wolf
authors: Stefan
authors: S
authors: Gattenlöhner
authors: Johann
authors: J
authors: Bauersachs
authors: Georg
authors: G
authors: Ertl
mesh_terms: D000818:Animals; D002921:Cicatrix / Q000473:pathology; D024042:Collagen Type I / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D005109:Extracellular Matrix / Q000235:genetics / Q000473:pathology; D006098:Granulocytes / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D009154:Mutation / Q000235:genetics*; D009203:Myocardial Infarction / Q000235:genetics* / Q000473:pathology; D010013:Osteogenesis Imperfecta / Q000235:genetics*; D012333:RNA, Messenger; D015996:Survival Rate; D018487:Ventricular Dysfunction, Left / Q000235:genetics / Q000473:pathology; D018658:Ventricular Septal Rupture / Q000235:genetics* / Q000473:pathology; D014945:Wound Healing / Q000235:genetics*
chemical_list: D024042:Collagen Type I; D012333:RNA, Messenger; D020780:Matrix Metalloproteinase 9