title: Anti-inflammatory peptides from cardiac progenitors ameliorate dysfunction after myocardial infarction.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, Japan (M.L.L., T.N., M.T., K.I., T.T., M.K., N.K., Y.K.).
authors.forename: Mei-Lan
authors.initials: ML
authors.lastname: Liu
authors.affiliation: Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, Japan (M.L.L., T.N., M.T., K.I., T.T., M.K., N.K., Y.K.).
authors.forename: Toshio
authors.initials: T
authors.lastname: Nagai
authors.affiliation: Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, Japan (M.L.L., T.N., M.T., K.I., T.T., M.K., N.K., Y.K.).
authors.forename: Masakuni
authors.initials: M
authors.lastname: Tokunaga
authors.affiliation: Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, Japan (M.L.L., T.N., M.T., K.I., T.T., M.K., N.K., Y.K.).
authors.forename: Koji
authors.initials: K
authors.lastname: Iwanaga
authors.affiliation: Department of Cardiology and Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Shinjuku-ku, Tokyo, Japan (K.M.).
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Matsuura
authors.affiliation: Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, Japan (M.L.L., T.N., M.T., K.I., T.T., M.K., N.K., Y.K.).
authors.forename: Toshinao
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, Japan (M.L.L., T.N., M.T., K.I., T.T., M.K., N.K., Y.K.).
authors.forename: Masato
authors.initials: M
authors.lastname: Kanda
authors.affiliation: Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, Japan (M.L.L., T.N., M.T., K.I., T.T., M.K., N.K., Y.K.).
authors.forename: Naomichi
authors.initials: N
authors.lastname: Kondo
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan (A.T.N., I.K.).
authors.forename: Atsuhiko T
authors.initials: AT
authors.lastname: Naito
authors.affiliation: Department of Cardiovascular Medicine, The University of Tokyo Graduate School of Medicine, Tokyo, Japan (A.T.N., I.K.).
authors.forename: Issei
authors.initials: I
authors.lastname: Komuro
authors.affiliation: Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, Japan (M.L.L., T.N., M.T., K.I., T.T., M.K., N.K., Y.K.).
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism*; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000378:metabolism; D004195:Disease Models, Animal; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000637:transplantation*; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000378:metabolism; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*; D057705:Transendothelial and Transepithelial Migration; D014162:Transfection; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D000893:Anti-Inflammatory Agents; D057134:Antibodies, Neutralizing; D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; C498686:F11r protein, mouse; D011956:Receptors, Cell Surface
keywords: cardiac progenitor cells; cell adhesion molecules; cell transplantation; inflammation; myocardial infarction