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

Cited 109 time in Web of Science Cited 128 time in Scopus
Issue Date
2007
Publisher
American Society of Hematology
Citation
Blood. 2007;110:3891-3899
Keywords
AnimalsE-Selectin/genetics/*metabolism/pharmacologyEndothelial Cells/*metabolism/pathologyHindlimb/blood supply/metabolism/pathologyInterleukin-8/biosynthesisIschemia/drug therapy/genetics/*metabolismMiceMice, KnockoutMuscle, Skeletal/blood supply/*metabolism/pathologyNeovascularization, Pathologic/drug therapy/genetics/*metabolismRNA, Small Interfering/genetics/pharmacologyStem Cell TransplantationStem CellsTime FactorsTransplantation, HomologousCell 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
DOI
https://doi.org/10.1182/blood-2006-10-048991
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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