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Temporal elevation of type VI collagen and cardiac myofibroblast differentiation during post‐infarction remodeling

Jennifer E. Naugle, Erik R. Olson, John C. Koshy, Donald J. Costic, Cheryl M. Hodnichak, C. F. Pilati, Kathleen J. Doane, J. Gary Meszaros

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Abstract

Cardiac fibroblasts and myofibroblasts are responsible for post‐myocardial infarction (MI) remodeling which occurs via regulation of extracellular matrix (ECM) production and composition. Myofibroblasts, which are hypersecretory fibroblasts involved in wound healing and repair, are typically activated immediately following an injury to the myocardium. We have reported that type VI collagen induces myofibroblast differentiation in isolated cultures of cardiac fibroblasts. The purpose of this study was to determine the temporal expression patterns of type VI collagen and myofibroblast content in early post‐MI remodeling. We have previously determined that type VI and myofibroblast content were both elevated 20 weeks post‐MI. Here we report significant increases in type VI collagen at both 7 and 14 days post‐MI, but not at 3 days. Elevation in myofibroblast content was observed at 7 days in the infarcted myocardium, but not at 3 or 14 days post‐MI. Thus, type VI collagen and myofibroblast content concurrently increase by day 7 post‐MI, and both are also elevated at 20 weeks post‐MI. Taken together, these data suggest that type VI collagen may play a causative role in post‐MI myofibroblast differentiation. This work is supported by the Ohio Board of Regents Grant #34177.

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What this paper is about

Cardiac fibroblasts and myofibroblasts are responsible for post‐myocardial infarction (MI) remodeling which occurs via regulation of extracellular matrix (ECM) production and composition. Myofibroblasts, which are hypersecretory fibroblasts involved in wound healing and repair, are typically activated immediately following an injury to the myocardium. We have reported that type VI collagen induces myofibroblast differentiation in isolated cultures of cardiac fibroblasts. The purpose of this study was to determine the temporal expression patterns of type VI collagen and myofibroblast content in early post‐MI remodeling. We have previously determined that type VI and myofibroblast content were both elevated 20 weeks post‐MI. Here we report significant increases in type VI collagen at both 7 and 14 days post‐MI, but not at 3 days. Elevation in myofibroblast content was observed at 7 days in the infarcted myocardium, but not at 3 or 14 days post‐MI. Thus, type VI collagen and myofibroblast content concurrently increase by day 7 post‐MI, and both are also elevated at 20 weeks post‐MI. Taken together, these data suggest that type VI collagen may play a causative role in post‐MI myofibroblast differentiation. This work is supported by the Ohio Board of Regents Grant #34177.

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Available abstract

Cardiac fibroblasts and myofibroblasts are responsible for post‐myocardial infarction (MI) remodeling which occurs via regulation of extracellular matrix (ECM) production and composition. Myofibroblasts, which are hypersecretory fibroblasts involved in wound healing and repair, are typically activated immediately following an injury to the myocardium. We have reported that type VI collagen induces myofibroblast differentiation in isolated cultures of cardiac fibroblasts. The purpose of this study was to determine the temporal expression patterns of type VI collagen and myofibroblast content in early post‐MI remodeling. We have previously determined that type VI and myofibroblast content were both elevated 20 weeks post‐MI. Here we report significant increases in type VI collagen at both 7 and 14 days post‐MI, but not at 3 days. Elevation in myofibroblast content was observed at 7 days in the infarcted myocardium, but not at 3 or 14 days post‐MI. Thus, type VI collagen and myofibroblast content concurrently increase by day 7 post‐MI, and both are also elevated at 20 weeks post‐MI. Taken together, these data suggest that type VI collagen may play a causative role in post‐MI myofibroblast differentiation. This work is supported by the Ohio Board of Regents Grant #34177.

Key concepts: Myofibroblast, Extracellular matrix, Wound healing, Myocardial infarction, Pathology, Type I collagen, Chemistry, Ventricular remodeling

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