title: The angiogenic factor CCN1 promotes adhesion and migration of circulating CD34+ progenitor cells: potential role in angiogenesis and endothelial regeneration.
abstract: Tissue regeneration involves the formation of new blood vessels regulated by angiogenic factors. We reported recently that the expression of the angiogenic factor CCN1 is up-regulated under various pathophysiologic conditions within the cardiovascular system. Because CD34+ progenitor cells participate in cardiovascular tissue regeneration, we investigated whether CCN1-detected for the first time in human plasma-promotes the recruitment of CD34+ progenitor cells to endothelial cells, thereby enhancing endothelial proliferation and neovascularization. In this study, we demonstrated that CCN1 and supernatants from CCN1-stimulated human CD34+ progenitor cells promoted proliferation of endothelial cells and angiogenesis in vitro and in vivo. In addition, CCN1 induced migration and transendothelial migration of CD34+ cells and the release of multiple growth factors, chemokines, and matrix metalloproteinase-9 (MMP-9) from these cells. Moreover, the CCN1-specific integrins alpha(M)beta(2) and alpha(V)beta(3) are expressed on CD34+ cells and CCN1 stimulated integrin-dependent signaling. Furthermore, integrin antagonists (RGD-peptides) suppressed both binding of CCN1 to CD34+ cells and CCN1-induced adhesion of CD34+ cells to endothelial cells. These data suggest that CCN1 promotes integrin-dependent recruitment of CD34+ progenitor cells to endothelial cells, which may contribute to paracrine effects on angiogenesis and tissue regeneration.
authors.affiliation: Department of Cardiology, Medical School Hannover, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany. grote.karsten@mh-hannover.de
authors.forename: Karsten
authors.initials: K
authors.lastname: Grote
authors.forename: Gustavo
authors.initials: G
authors.lastname: Salguero
authors.forename: Matthias
authors.initials: M
authors.lastname: Ballmaier
authors.forename: Marc
authors.initials: M
authors.lastname: Dangers
authors.forename: Helmut
authors.initials: H
authors.lastname: Drexler
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schieffer
mesh_terms: D000818:Animals; D018952:Antigens, CD34; D000970:Antineoplastic Agents / Q000494:pharmacology; D002319:Cardiovascular System / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D055515:Cysteine-Rich Protein 61; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism* / Q000494:pharmacology; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism* / Q000494:pharmacology; D016177:Macrophage-1 Antigen / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D019899:Paracrine Communication / Q000187:drug effects / Q000502:physiology*; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D018952:Antigens, CD34; D000970:Antineoplastic Agents; C501848:CCN1 protein, human; D055515:Cysteine-Rich Protein 61; D017874:Immediate-Early Proteins; D039302:Integrin alphaVbeta3; D036341:Intercellular Signaling Peptides and Proteins; D016177:Macrophage-1 Antigen; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D020780:Matrix Metalloproteinase 9