Endothelial E-selectin potentiates neovascularization via endothelial progenitor cell-dependent and -independent mechanisms.
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.


RESULTS
Peripheral blood mononuclear cells were isolated from healthy volunteers and cultured for 7 days to obtain EPCs. Tumor necrosis factor-alpha-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 beta-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.
Nishiwaki
Yasunobu
Y
Department of Cardiovascular Medicine, Tokyo Medical and Dental University, School of Medicine, Tokyo, Japan.
Yoshida
Masayuki
M
Iwaguro
Hideki
H
Masuda
Haruchika
H
Nitta
Noriko
N
Asahara
Takayuki
T
Isobe
Mitsuaki
M
D000704:Analysis of Variance; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D019040:E-Selectin / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D011336:Probability; D012680:Sensitivity and Specificity; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D019040:E-Selectin; D014409:Tumor Necrosis Factor-alpha