Document Detail


Therapeutic Angiogenesis of Human Early Endothelial Progenitor Cells Is Enhanced by Thrombomodulin.
MedLine Citation:
PMID:  21836068     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
OBJECTIVE: We examined the effect of thrombomodulin (TM) domains 2 and 3 (TMD23) on human early endothelial progenitor cells (EPCs). METHODS AND RESULTS: TM was expressed and released by human EPCs cultured from peripheral blood mononuclear cells (PBMCs). Addition of TMD23 (100 ng/mL) to the cultured PBMCs increased the colony-forming units, chemotactic motility, matrix metalloproteinase activity, and interleukin-8 secretion but decreased tumor necrosis factor-α (TNF-α) release. Analysis of the signal pathway showed that TMD23 activated Akt. Inhibition of phosphatidylinositol-3 kinase-Akt blocked the effects of TMD23 on chemotactic motility, matrix metalloproteinase-9, interleukin-8, and TNF-α. In hindlimb ischemia mice, laser Doppler perfusion imaging of the ischemic limb during the 21 days after arterial ligation showed that the perfusion recovered best with intraperitoneal infusion of TMD23 plus local injection of early EPCs, followed by either infusion of TMD23 or injection of the cells. Animals without either treatment had the worst results. Animals treated with TMD23 also had lower circulating and tissue levels of TNF-α. CONCLUSIONS: TM is expressed and released by human circulating EPCs. Exogenous TMD23 enhances the angiogenic potential of early EPCs in vitro through activation of phosphatidylinositol-3 kinase-Akt pathway. Coadministration of TMD23 plus early EPCs augments therapeutic angiogenesis of the EPCs in ischemic tissues.
Authors:
Jiun-Yi Li; Cheng-Huang Su; Yih-Jer Wu; Ting-Yi Tien; Chin-Ling Hsieh; Chih-Hao Chen; Ya-Ming Tseng; Guey-Yueh Shi; Hua-Lin Wu; Cheng-Ho Tsai; Fang-Yue Lin; Hung-I Yeh
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-8-11
Journal Detail:
Title:  Arteriosclerosis, thrombosis, and vascular biology     Volume:  -     ISSN:  1524-4636     ISO Abbreviation:  -     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-8-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9505803     Medline TA:  Arterioscler Thromb Vasc Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Departments of Surgery.
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