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Cell Therapy Limits Myofibroblast Differentiation and Structural Cardiac Remodeling: bFGF-Mediated Paracrine Mechanism.
MedLine Citation:
PMID:  22508775     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 borderzone of subacute infarcted syngeneic Fischer rat hearts and compared to medium-injected controls. 12 weeks post-injection, cell-treated hearts showed preserved ECM content and attenuated structural chamber remodeling. Myofibroblast activation (α-smooth muscle actin expression) was significantly decreased while bFGF expression, a known inhibitor of TGFβ1-induced fibroblast differentiation, was increased. MMP-2 expression and activation by gelatin zymography was unchanged between groups while its endogenous inhibitor, 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: -ECM dysregulation post-MI 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.
Authors:
Paul W M Fedak; Liping Bai; Jeannine Turnbull; Janet Ngu; Kishan Narine; Henry J Duff
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-4-16
Journal Detail:
Title:  Circulation. Heart failure     Volume:  -     ISSN:  1941-3297     ISO Abbreviation:  -     Publication Date:  2012 Apr 
Date Detail:
Created Date:  2012-4-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101479941     Medline TA:  Circ Heart Fail     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Libin Cardiovascular Institute of Alberta, Calgary, Canada.
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