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Involvement of E-selectin in recruitment of endothelial progenitor cells and angiogenesis in ischemic muscle
Cited 114 time in
Web of Science
Cited 134 time in Scopus
- Authors
- Issue Date
- 2007
- Publisher
- American Society of Hematology
- Citation
- Blood. 2007;110:3891-3899
- Keywords
- Animals ; 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 ; Cell Movement
- 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.
- ISSN
- 0006-4971 (Print)
- Language
- English
- URI
- http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17699745
https://hdl.handle.net/10371/24890
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