Type VI collagen induces cardiac myofibroblast differentiation: implications for postinfarction remodeling

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 290; no. 1; pp. H323 - H330
• Main Authors: Naugle, Jennifer E, Olson, Erik R, Zhang, Xiaojin, Mase, Sharon E, Pilati, Charles F, Maron, Michael B, Folkesson, Hans G, Horne, Walter I, Doane, Kathleen J, Meszaros, J. Gary
• Format: Journal Article
• Language: English
• Published: United States 01.01.2006
• Subjects: Angiotensin II - pharmacology; Animals; Cell Differentiation - drug effects; Cell Proliferation - drug effects; Cells, Cultured; Collagen Type I - physiology; Collagen Type III - physiology; Collagen Type VI - physiology; Coronary Vessels - pathology; Extracellular Matrix - physiology; Fibroblasts - cytology; Fibrosis - etiology; Ligation; Male; Myocardial Infarction - physiopathology; Rats; Rats, Sprague-Dawley; Ventricular Remodeling - physiology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00321.2005

Departments of 1 Physiology and Pharmacology and 2 Anatomy; and 3 Comparative Medicine Unit, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio Submitted 31 March 2005 ; accepted in final form 1 September 2005 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. cardiac fibroblasts; fibrosis; extracellular matrix; -smooth muscle actin Address for reprint requests and other correspondence: J. G. Meszaros, Northeastern Ohio Universities College of Medicine, Dept. of Physiology and Pharmacology, 4209 State Rte. 44, Rootstown, OH 44272-0095 (e-mail: jgmeszar{at}neoucom.edu )