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Blood, 1 August 2007, Vol. 110, No. 3, pp. 877-885. Prepublished online as a Blood First Edition Paper on April 11, 2007; DOI 10.1182/blood-2006-07-036202.
Submitted July 19, 2006
Dept of Cardiology & Angiology, Medical School Hannover, Hannover, Germany * Corresponding author; email: grote.karsten{at}mh-hannover.de.
Tissue regeneration involves the formation of new blood vessels regulated by angiogenic factors. We recently reported that the expression of the angiogenic factor CCN1 is up-regulated under various pathophysiological conditions within the cardiovascular system. Since CD34+ progenitor cells participate in cardiovascular tissue regeneration, we investigated if CCN1--which we first time detected in human plasma--promotes the recruitment of CD34+ progenitor cells to endothelial cells thereby enhancing endothelial proliferation and neo-vascularization. Here, we demonstrate 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
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