Cardiac myofibroblast differentiation is attenuated by alpha(3) integrin blockade: potential role in post-MI remodeling.

Title

Cardiac myofibroblast differentiation is attenuated by alpha(3) integrin blockade: potential role in post-MI remodeling.

Creator

Bryant Jennifer E; Shamhart Patricia E; Luther Daniel J; Olson Erik R; Koshy John C; Costic Donald J; Mohile Monica V; Dockry Michelle; Doane Kathleen J; Meszaros J Gary

Publisher

Journal of molecular and cellular cardiology

Date

2009
2009-02

Description

Cardiac fibroblasts and myofibroblasts are responsible for post-MI remodeling which occurs via regulation of extracellular matrix (ECM). Accelerated post-MI remodeling leads to excessive ECM deposition and fibrosis, contributing to impaired contractile function, arrhythmias, and heart failure. We have previously reported that type VI collagen induces myofibroblast differentiation in cultured cardiac fibroblasts, and that type VI collagen and myofibroblast content were both elevated in the myocardium 20 weeks post-MI. The purpose of this study was to determine the expression patterns of type VI collagen and myofibroblast content in early post-myocardial infarction (MI) remodeling to gain insight into whether type VI collagen induces in vivo myofibroblast differentiation via specific matrix-receptor interactions. Adult male Sprague-Dawley rats were anesthetized and left coronary arteries were permanently ligated. Histological tissue sections and whole tissue protein lysates were obtained from infarcted and non-infarcted areas of MI hearts and sham operated controls. At 3 days post-MI, we observed a significant increase in alpha(3) integrin expression (2.02+/-0.18 fold); at 7 days post-infarction both type VI collagen (2.27+/-0.18 fold) and myofibroblast (4.65+/-0.6 fold) content increased. By 14 days myofibroblast content returned to sham control levels, although type VI collagen (2.42+/-0.11 fold) was still elevated. In vitro cross-linking confirmed that the alpha(3) integrin interacts with type VI collagen, and alpha(3) integrin function blocking antibodies inhibited the differentiation of isolated cardiac fibroblasts. Collectively, our in vitro results indicate that the alpha(3) integrin receptor interacts with type VI collagen to promote myofibroblast differentiation, and that this interaction may impact in vivo post-MI remodeling.

Subject

Animals; Cell Differentiation/*physiology; Collagen Type VI/*metabolism/physiology; Fibroblasts/*cytology; Immunoblotting; Integrin alpha3/*metabolism; Male; Myocardial Infarction/*metabolism; Myocardium/*cytology; Protein Binding; Rats

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Pages

186–192

Issue

2

Volume

46

Citation

Bryant Jennifer E; Shamhart Patricia E; Luther Daniel J; Olson Erik R; Koshy John C; Costic Donald J; Mohile Monica V; Dockry Michelle; Doane Kathleen J; Meszaros J Gary, “Cardiac myofibroblast differentiation is attenuated by alpha(3) integrin blockade: potential role in post-MI remodeling.,” NEOMED Bibliography Database, accessed May 20, 2022, https://neomed.omeka.net/items/show/3820.

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