Abstract 11252: Anti-inflammatory Peptides Secreted from Cardiac Progenitor Cells Ameliorates Cardiac Dysfunction after Myocardial Infarction
Regenerative therapy based on cell engraftment into the infarct heart has been proposed as one of the new strategies against myocardial infarction. Although several reports showed that engrafted cells improve the function of ischemic heart, the effects of cell therapy are variable among the studies and the mechanisms of the beneficial effects are still unknown. From the engraftment of various cell types, we found that clonal stem cell antigen-1 positive cardiac progenitor cells (CPC) were the only cell type that exerted therapeutic effects. By using antibody array we found that soluble form of junctional adhesion molecule-A (JAM-A) was abundantly secreted from CPC. JAM-A is one of the constituents of tight junction and its soluble form was known to block transendothelial migration and attenutae inflammatory response. Pretreatment of neutrophil with CPC conditioned medium inhibited tumor necrosis factor-alpha-induced transendothelial migration and this inhibitory effect was attenuated by neutralizing anti-JAM-A antibody. Immunohistochemical and quantitative real-time PCR analysis showed that injection of CPC into infarct heart reduce % of Ly6G-positive neutrophil to total cells (control: 18.6±4.5%; CPC: 10.2±3.9%), and expression of neutrophil marker gene (Ly6G: 104±21.7 and 59.5±23.7, control and CPC, respectively; myeroperoxidase: 22.2±2.1 and 14.6±1.9, control and CPC, respectively) and tumor necrosis factor-alpha (control: 3.11±0.04; CPC: 1.24±0.20) in comparison with non-treated control. Injection of JAM-A protein but not JAM-A siRNA expressing CPC into the infarct area reduced expression of Ly6G gene (control: 86.8±15.8; JAM-A: 43.1±30.8; JAM-A siRNA: 101.8±48.4) and reduced fibrosis area (control: 36.3±9.3%; JAM-A: 25.2±15.0%; JAM-A siRNA: 37.5±48.4%) in comparison with non-treated control. Thus soluble form of JAM-A secreted from CPC blocks transendothelial migration of inflammatory cells after myocardial infarction and ameliorates tissue damage to the infarct heart through prevention of excess inflammation. Our finding may lead to establish a new therapy for cardiovascular disease by utilizing the anti-inflammatory effect of JAM-A.
- © 2012 by American Heart Association, Inc.