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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:512.)
© 2007 American Heart Association, Inc.

Vascular Biology

Endothelial E-Selectin Potentiates Neovascularization via Endothelial Progenitor Cell–Dependent and –Independent Mechanisms

Yasunobu Nishiwaki; Masayuki Yoshida; Hideki Iwaguro; Haruchika Masuda; Noriko Nitta; Takayuki Asahara; Mitsuaki Isobe

From Department of Cardiovascular Medicine (Y.N., M.I.), Tokyo Medical and Dental University, School of Medicine, Tokyo, Japan; Department of Medical Biochemistry (Y.N., M.Y., N.N.), Tokyo Medical and Dental University, School of Medicine, Tokyo, Japan; Department of Regenerative Medicine (H.I., H.M., T.A.), Tokai University, School of Medicine, Kanagawa, Japan.

Correspondence to Masayuki Yoshida, 1-5-45,Yushima D9, Bunkyo-ku, Tokyo, 113-8519 Japan. E-mail masavasc{at}tmd.ac.jp

Background— Although potential participation of bone marrow-derived circulating endothelial progenitor cells (EPCs) to neoangiogenesis has been proposed, the precise molecular mechanisms of EPC recruitment to vascular endothelium has not been fully elucidated.

Methods and Results— Peripheral blood mononuclear cells were isolated from healthy volunteers and cultured for 7 days to obtain EPCs. Tumor necrosis factor-–activated human umbilical vein endothelial cells (HUVECs) supported significantly more rolling and adhesion of EPCs compared with inactivated HUVEC monolayer. Pretreatment of activated HUVEC with an adhesion-blocking mAb to E-selectin significantly reduced EPCs adhesion to HUVECs. When HUVECs were transduced with a recombinant adenovirus of E-selectin (AdRSVE-sel) or that of ß-galactosidase (AdRSVLacZ), E-selectin-transduced but not LacZ-transduced HUVECs exhibited significantly more EPC rolling as well as adhesion. Further, effect of AdRSVE-sel or AdRSVLacZ was examined in mouse hind limb ischemic model. AdRSVE-sel–transduced mice showed significantly less limb necrosis and higher laser Doppler ratio when compared with AdRSVLacZ-transduced mice. Interestingly, blood flow recovery of ischemic limb observed in AdRSVE-sel–transduced mice was more prominent when combined with EPC administration compared with that of AdRSVLacZ-transduced mice.

Conclusions— Endothelial E-selectin plays a crucial role in EPC–endothelial interaction in vitro. The importance of E-selectin was also confirmed in vivo even in the absence of exogenous EPC. These data provide molecular background for novel cell-based therapy for ischemic atherosclerosis.

Although potential participation of bone marrow-derived circulating endothelial progenitor cells (EPCs) to neoangiogenesis has been proposed, the precise molecular mechanisms of EPC recruitment to vascular endothelium has not been fully elucidated.

Key Words: angiogenesis • adhesion molecule • endothelial cell

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