Affiliation:
1. From the Department of Cardiac Sciences, University of Calgary, Libin Cardiovascular Institute of Alberta, Alberta, Canada. Liping Bai was affiliated with Libin Cardiovascular Institute of Alberta at the time that this work was completed.
Abstract
Background—
Experimental cell therapy attenuates maladaptive cardiac remodeling and improves heart function. Paracrine mechanisms have been proposed. The effect of cell therapy on post infarction cardiac fibroblast and extracellular matrix (ECM) regulation was examined.
Methods and Results—
Vascular smooth muscle cells (VSMC) were injected into the border zone of subacute infarcted syngeneic Fischer rat hearts and compared with medium-injected controls. Twelve weeks post injection, cell-treated hearts showed preserved ECM content and attenuated structural chamber remodeling. Myofibroblast activation (α-smooth muscle actin expression) was decreased significantly, while basic fibroblast growth factor (bFGF) expression, a known inhibitor of transforming growth factor β-1–induced fibroblast differentiation, was increased. Matrix metalloproteinase-2 expression and activation by gelatin zymography was unchanged between groups, while its endogenous inhibitor, tissue inhibitors of matrix metalloproteinase (TIMP)-2, showed both increased expression and enhanced inhibitory capacity in cell-treated hearts. To define paracrine mechanisms, in vitro effects of VSMC conditioned media on myofibroblast activation were assessed by 3-D collagen gel contraction assay. VSMC conditioned media significantly inhibited collagen contraction, while a specific bFGF inhibitor abolished this paracrine response. TIMP-2 induced collagen contraction, but the effect was suppressed in the presence of bFGF.
Conclusions—
Extracellular matrix dysregulation post myocardial infarction is improved by cell therapy. These data suggest that cell transplantation attenuates myofibroblast activation and subsequent maladaptive structural chamber remodeling through paracrine mechanisms involving bFGF and TIMP-2.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine
Cited by
28 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献