S-Space College of Medicine/School of Medicine (의과대학/대학원) Internal Medicine (내과학전공) Journal Papers (저널논문_내과학전공)
Involvement of E-selectin in recruitment of endothelial progenitor cells and angiogenesis in ischemic muscle
- Oh, Il-Young; Yoon, Chang-Hwan; Hur, Jin; Kim, Ji-Hyun; Kim, Tae-Youn; Lee, Choon-Soo; Park, Kyung-Woo; Chae, In-Ho; Oh, Byung-Hee; Park, Young-Bae; Kim, Hyo-Soo
- Issue Date
- American Society of Hematology
- Blood. 2007;110:3891-3899
- Animals; *Cell Movement; E-Selectin/genetics/*metabolism/pharmacology; Endothelial Cells/*metabolism/pathology; Hindlimb/blood supply/metabolism/pathology; Interleukin-8/biosynthesis; Ischemia/drug therapy/genetics/*metabolism; Mice; Mice, Knockout; Muscle, Skeletal/blood supply/*metabolism/pathology; Neovascularization, Pathologic/drug therapy/genetics/*metabolism; RNA, Small Interfering/genetics/pharmacology; Stem Cell Transplantation; Stem Cells; Time Factors; Transplantation, Homologous
- E-selectin plays critical roles in tethering leukocytes to endothelial cells (ECs). We studied the role of E-selectin in endothelial progenitor cell (EPC) homing and vasculogenesis. After ischemia, the expression of E-selectin on ECs peaked 6 to 12 hours and returned to baseline at 24 hours, whereas the level of soluble E-selectin (sE-selectin) in serum increased over 24 hours and remained high at day 7. Mouse bone marrow-derived EPCs expressed not only E-selectin but also its ligand. Homing of circulating EPCs to ischemic limb was significantly impaired in E-selectin knock-out mice, as well as wild-type mice pretreated with blocking antibody against E-selectin, which was rescued by local sE-selectin injection. Mechanism for this is that sE-selectin stimulated not only ECs to express ICAM-1, but also EPCs to secrete interleukin-8 (IL-8), leading to enhanced migration and incorporation to ECs capillary formation. In therapeutic aspect, local treatment with sE-selectin enhanced efficacy of EPC transplantation for vasculogenesis and salvage of ischemic limb. Conversely, when E-selectin was knocked down by E-selectin small interfering RNA, blood flow recovery after EPC transplantation was significantly impaired. But this impaired vasculogenesis was rescued by sE-selectin. In conclusion, these data demonstrate E-selectin is a pivotal molecule for EPCs' homing to ischemic limb and vasculogenesis.
- 0006-4971 (Print)
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