title: Type VI collagen induces cardiac myofibroblast differentiation: implications for postinfarction remodeling.
abstract: Cardiac fibroblast (CF) proliferation and differentiation into hypersecretory myofibroblasts can lead to excessive extracellular matrix (ECM) production and cardiac fibrosis. In turn, the ECM produced can potentially activate CFs via distinct feedback mechanisms. To assess how specific ECM components influence CF activation, isolated CFs were plated on specific collagen substrates (type I, III, and VI collagens) before functional assays were carried out. The type VI collagen substrate potently induced myofibroblast differentiation but had little effect on CF proliferation. Conversely, the type I and III collagen substrates did not affect differentiation but caused significant induction of proliferation (type I, 240.7 +/- 10.3%, and type III, 271.7 +/- 21.8% of basal). Type I collagen activated ERK1/2, whereas type III collagen did not. Treatment of CFs with angiotensin II, a potent mitogen of CFs, enhanced the growth observed on types I and III collagen but not on the type VI collagen substrate. Using an in vivo model of myocardial infarction (MI), we measured changes in type VI collagen expression and myofibroblast differentiation after post-MI remodeling. Concurrent elevations in type VI collagen and myofibroblast content were evident in the infarcted myocardium 20-wk post-MI. Overall, types I and III collagen stimulate CF proliferation, whereas type VI collagen plays a potentially novel role in cardiac remodeling through facilitation of myofibroblast differentiation.
authors.affiliation: Northeastern Ohio Universities College of Medicine, Dept. of Physiology and Pharmacology, 4209 State Rte. 44, Rootstown, OH 44272-0095, USA.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Naugle
authors.forename: Erik R
authors.initials: ER
authors.lastname: Olson
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Zhang
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Mase
authors.forename: Charles F
authors.initials: CF
authors.lastname: Pilati
authors.forename: Michael B
authors.initials: MB
authors.lastname: Maron
authors.forename: Hans G
authors.initials: HG
authors.lastname: Folkesson
authors.forename: Walter I
authors.initials: WI
authors.lastname: Horne
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Doane
authors.forename: J Gary
authors.initials: JG
authors.lastname: Meszaros
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000502:physiology; D024061:Collagen Type III / Q000502:physiology; D024142:Collagen Type VI / Q000502:physiology*; D003331:Coronary Vessels / Q000473:pathology; D005109:Extracellular Matrix / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology*; D005355:Fibrosis / Q000209:etiology; D008026:Ligation; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D024142:Collagen Type VI; D000804:Angiotensin II