Alterations in cultured myocardial fibroblast function following the development of left ventricular failure

English C. Flack, Merry L. Lindsey, Christina E. Squires, Brooke S. Kaplan, Robert E. Stroud, Leslie L. Clark, Patricia G. Escobar, William M. Yarbrough, Francis G. Spinale

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

A structural event in the progression of left ventricular (LV) failure is myocardial extracellular matrix (ECM) remodeling. The myocardial fibroblast is a major cell type influencing the ECM, but whether and to what degree specific phenotypic differences in myocardial fibroblasts can be demonstrated to occur in culture with the development of LV failure remains unclear. Adult pigs (25 kg) were used for control myocardial fibroblast preparations (N = 5) or following pacing-induced LV failure (N = 5; 240 bpm, 3 weeks). LV remodeling occurred with pacing as evidenced by increased LV end diastolic volume (132 ± 11 vs. 60 ± 4 mL for control; P < 0.05). Functional parameters including migration, adhesion, collagen and matrix metalloproteinase release were assessed in fibroblast cultures from passages 1-4. The following findings were consistent with each passage and the results were analyzed with control values set to 100%. Migration of LV failure fibroblasts increased by over 170% (P < 0.05). Adhesion to collagen I, laminin and fibronectin was increased by over 160% in LV failure fibroblasts (P < 0.05). β1 integrin density decreased by 50% in LV failure fibroblasts (P < 0.05). Fibrillar collagen release increased by over 130% and matrix metalloproteinase-2 increased by 140% in LV failure fibroblasts (P < 0.05). The unique findings of this study are two-fold. First, after a pathological stimulus in-vivo, adult myocardial fibroblasts maintain a consistent phenotype through early passages in-vivo. Second, a differential release of, and response to ECM components occurred in LV failure fibroblasts. Thus, a phenotypic transformation of the myocardial fibroblast occurs with the development of LV failure, which in turn may contribute to matrix remodeling and presents as a potential cellular therapeutic target.

Original languageEnglish (US)
Pages (from-to)474-483
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume40
Issue number4
DOIs
StatePublished - Apr 2006

Keywords

  • Fibroblast migration
  • Heart failure
  • Integrins
  • Matrix metalloproteinases
  • Myocardial matrix

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

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    Flack, E. C., Lindsey, M. L., Squires, C. E., Kaplan, B. S., Stroud, R. E., Clark, L. L., Escobar, P. G., Yarbrough, W. M., & Spinale, F. G. (2006). Alterations in cultured myocardial fibroblast function following the development of left ventricular failure. Journal of Molecular and Cellular Cardiology, 40(4), 474-483. https://doi.org/10.1016/j.yjmcc.2006.01.019