Altered fibroblast function following myocardial infarction

Christina E. Squires, G. Patricia Escobar, John F. Payne, Robert A. Leonardi, Danielle K. Goshorn, Nina J. Sheats, I. Matthew Mains, Joseph T. Mingoia, English C. Flack, Merry L. Lindsey

Research output: Contribution to journalArticle

94 Scopus citations

Abstract

Adequate wound healing and scar formation is an essential response to myocardial infarction (MI), and fibroblasts are primary cellular components regulating the process. How fibroblast functions are altered post-MI and to what extent these abnormalities persist in vitro is not well understood. Accordingly, we isolated myocardial fibroblasts from MI and non-MI (remote) regions at 7:days post-MI (n = 35) and from the free wall and septum of unoperated control C57BL/6 mice (n = 14). Proliferation was increased 182 ± 28% in MI, but not in remote, fibroblasts compared with unoperated controls (P = 0.01). Migration decreased 61 ± 8%, adhesion to laminin decreased 79 ± 8%, adhesion to collagen IV increased 196 ± 27%, and collagen synthesis increased 169 ± 24% in fibroblasts isolated from the MI region (all P < 0.05). Migration, adhesion, and collagen synthesis changes were similar in remote fibroblasts, and the phenotypic differences were maintained through passage four. Transforming growth factor β1 (TGFβ1) is a bioactive molecule that has been shown to affect fibroblast function. Stimulation of unoperated control fibroblasts with 10:ng/ml TGFβ 1 increased proliferation 137 ± 7% (P = 0.03 vs. unstimulated), increased adhesion to collagen IV 149 ± 6% (P < 0.01), and increased collagen I levels 187 ± 10% (P = 0.01). TGFβ1 may, therefore, explain some of the changes in post-MI fibroblast phenotype. These data demonstrate for the first time region specific alterations in post-MI fibroblast biology that are maintained in vitro. Additionally, our model provides a novel in vitro template for examining the cellular mechanisms of wound healing and scar formation post-MI.

Original languageEnglish (US)
Pages (from-to)699-707
Number of pages9
JournalJournal of Molecular and Cellular Cardiology
Volume39
Issue number4
DOIs
StatePublished - Oct 2005

Keywords

  • Adhesion
  • Fibroblast
  • Mice
  • Migration
  • Myocardial infarction
  • Proliferation

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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    Squires, C. E., Escobar, G. P., Payne, J. F., Leonardi, R. A., Goshorn, D. K., Sheats, N. J., Mains, I. M., Mingoia, J. T., Flack, E. C., & Lindsey, M. L. (2005). Altered fibroblast function following myocardial infarction. Journal of Molecular and Cellular Cardiology, 39(4), 699-707. https://doi.org/10.1016/j.yjmcc.2005.07.008