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.
- Myocardial infarction
ASJC Scopus subject areas
- Molecular Biology
- Cardiology and Cardiovascular Medicine