Anti‐Inflammatory Peptides From Cardiac Progenitors Ameliorate Dysfunction After Myocardial Infarction

• Published in: Journal of the American Heart Association 2014-12, Vol.3 (6), p.e001101-n/a
• Main Authors: Liu, Mei‐Lan, Nagai, Toshio, Tokunaga, Masakuni, Iwanaga, Koji, Matsuura, Katsuhisa, Takahashi, Toshinao, Kanda, Masato, Kondo, Naomichi, Naito, Atsuhiko T., Komuro, Issei, Kobayashi, Yoshio
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - metabolism; Antibodies, Neutralizing - pharmacology; cardiac progenitor cells; cell adhesion molecules; Cell Adhesion Molecules - antagonists & inhibitors; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; cell transplantation; Cells, Cultured; Coculture Techniques; Culture Media, Conditioned - metabolism; Disease Models, Animal; inflammation; Inflammation - metabolism; Inflammation - pathology; Inflammation - physiopathology; Inflammation - prevention & control; Mice, Inbred C57BL; myocardial infarction; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Myocardial Infarction - surgery; Myocardium - metabolism; Myocardium - pathology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Myocytes, Cardiac - transplantation; Neutrophil Infiltration; Neutrophils - metabolism; Original Research; Receptors, Cell Surface - antagonists & inhibitors; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; RNA Interference; Stem Cell Transplantation - methods; Stem Cells - drug effects; Stem Cells - metabolism; Transendothelial and Transepithelial Migration; Transfection; Ventricular Function, Left; Ventricular Remodeling
• ISSN: 2047-9980; 2047-9980
• DOI: 10.1161/JAHA.114.001101

Background Cardiac cell therapy has been proposed as one of the new strategies against myocardial infarction. Although several reports showed improvement of the function of ischemic heart, the effects of cell therapy vary among the studies and the mechanisms of the beneficial effects are still unknown. Previously, we reported that clonal stem cell antigen‐1–positive cardiac progenitor cells exerted a therapeutic effect when transplanted into the ischemic heart. Our aims were to identify the cardiac progenitor‐specific paracrine factor and to elucidate the mechanism of its beneficial effect. Methods and Results By using an antibody array, we found that soluble junctional adhesion molecule‐A (JAM‐A) was abundantly secreted from cardiac progenitor cells. Pretreatment of neutrophils with conditioned medium from cultured cardiac progenitor cells or soluble JAM‐A inhibited transendothelial migration and reduced motility of neutrophils. These inhibitory effects were attenuated by anti–JAM‐A neutralizing antibody. Injection of cardiac progenitor cells into infarct heart attenuated neutrophil infiltration and expression of inflammatory cytokines. Injection of soluble JAM‐A–expressing, but not of JAM‐A siRNA–expressing, cardiac progenitor cells into the infarct heart prevented cardiac remodeling and reduced fibrosis area. Conclusions Soluble JAM‐A secreted from cardiac progenitor cells reduces infiltration of neutrophils after myocardial infarction and ameliorates tissue damage through prevention of excess inflammation. Our finding may lead to a new therapy for cardiovascular disease by using the anti‐inflammatory effect of JAM‐A.