Involvement of E-selectin in recruitment of endothelial progenitor cells and angiogenesis in ischemic muscle

Il Young Oh, Chang Hwan Yoon, Jin Hur, Ji Hyun Kim, Tae Youn Kim, Choon Soo Lee, Kyung Woo Park, In Ho Chae, Byung Hee Oh, Young Bae Park, Hyo Soo Kim

Research output: Contribution to journalArticlepeer-review

147 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)3891-3899
Number of pages9
JournalBlood
Volume110
Issue number12
DOIs
StatePublished - 1 Dec 2007

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