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(Circulation Research. 2008;102:356.)
© 2008 American Heart Association, Inc.

Cellular Biology

Adenosine Receptor–Mediated Adhesion of Endothelial Progenitors to Cardiac Microvascular Endothelial Cells

Sergey Ryzhov, Nataliya V. Solenkova, Anna E. Goldstein, Mathias Lamparter, Todd Fleenor, Pampee P. Young, James P. Greelish, John G. Byrne, Douglas E. Vaughan, Italo Biaggioni, Antonis K. Hatzopoulos, Igor Feoktistov

From the Departments of Medicine (S.R., M.L., P.P.Y, D.E.V., I.B., A.K.H., I.F), Pathology (P.P.Y.), Pharmacology (A.E.G, D.E.V., I.B., I.F), Cell and Developmental Biology (A.K.H) and Cardiac Surgery (N.V.S, T.F., J.P.G., J.G.B.), Vanderbilt University; and Veterans Medical Center (P.P.Y.), Nashville, Tenn.

Correspondence to Igor Feoktistov, 360 PRB, 2220 Pierce Ave, Nashville, TN 7232-6300. E-mail igor.feoktistov{at}vanderbilt.edu

Intracoronary delivery of endothelial progenitor cells (EPCs) is an emerging concept for the treatment of cardiovascular disease. Enhancement of EPC adhesion to vascular endothelium could improve cell retention within targeted organs. Because extracellular adenosine is elevated at sites of ischemia and stimulates neovascularization, we examined the potential role of adenosine in augmenting EPC retention to cardiac microvascular endothelium. Stimulation of adenosine receptors in murine embryonic EPCs (eEPCs) and cardiac endothelial cells (cECs) rapidly, within minutes, increased eEPC adhesion to cECs under static and flow conditions. Similarly, adhesion of human adult culture-expanded EPCs to human cECs was increased by stimulation of adenosine receptors. Furthermore, adenosine increased eEPC retention in isolated mouse hearts perfused with eEPCs. We determined that eEPCs and cECs preferentially express functional A₁ and A_2B adenosine receptor subtypes, respectively, and that both subtypes are involved in the regulation of eEPC adhesion to cECs. We documented that the interaction between P-selectin and its ligand (P-selectin glycoprotein ligand-1) plays a role in adenosine-dependent eEPC adhesion to cECs and that stimulation of adenosine receptors in cECs induces rapid cell surface expression of P-selectin. Our results suggest a role for adenosine in vasculogenesis and its potential use to stimulate engraftment in cell-based therapies.

Key Words: adenosine • adenosine receptors • endothelium • adhesion molecules

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