摘要
Cardiac fibroblasts constitute the predominant cell type in the interstitium of the remodeling heart and play an essential role in the response to infarction. In this study, the effects of a collagen-chitosan matrix on cardiac fibroblast phenotype (in vitro) and cardiac remodeling (in vivo) were investigated. Mouse cardiac fibroblasts were cultured on fibronectin, collagen or collagen-chitosan matrix, and fibroblast phenotype was assessed in vitro. Fibroblasts on the collagen-chitosan matrix had a reduced number of alpha-SMA(+) cells and less deposition of fibrillar collagen, indicative of less myofibroblast differentiation. For in vivo experiments, 2 weeks after myocardial infarction (MI), mice were randomly allocated to receive local injections of collagen-chitosan matrix, collagen matrix or phosphate buffered saline. Cardiac function parameters (left ventricular ejection fraction and fractional shortening) were improved only in collagen-chitosan injected mice over a 3-week followup period. The collagen-chitosan matrix-treated hearts also had smaller infarct size, higher arteriole density, reduced CD68(+) cell infiltration, and decreased matrix metalloproteinase-9 and elevated tissue inhibitor of metalloproteinase-2 levels compared to the other groups. This study demonstrates the potential of the collagen-chitosan matrix for use as a stand-alone therapy to regulate cardiac fibroblasts, alter remodeling and enhance function of the MI heart.
- 出版日期2014-11