期刊
THROMBOSIS RESEARCH
卷 126, 期 3, 页码 166-174出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.thromres.2010.03.002
关键词
EPC; Diabetes mellitus; OxLDL; Hyperglycemia; SDF1 alpha; Nitric oxide
资金
- Israel Ministry of Science Culture Sport
- Planning and Finance Committee for Higher Education
- Israel Science Foundation [1831/07]
- Mallat Family Award for Biomedical Research
- San Francisco Diabetes Research Fund
- Samuel Mendel Chodowsky Fund
- Chief Scientist Office of the Ministry of Health, Israel
Introduction: Type 2 diabetes mellitus (DM) patients with coronary artery disease (CAD) have elevated plasma oxidized-LDL (OxLDL) levels and impaired neovascularization. Hyperglycemia and hyperlipidemia impair endothelial progenitor cell (EPC) migration, and endothelial nitric oxide (NO) bioavailability and NO synthase (NOS) activity are essential for EPC migration. Stromal-derived factor-1 alpha (SDF1 alpha) contributes to EPC mobilization and homing by stimulating the CXC receptor-4 (CXCR4) on the EPC plasmalemma to activate the Pi3K/Akt/eNOS signaling pathway. Therefore, we investigated the effect of high glucose (HG) and OxLDL on the migration and NO bioavailability of EPCs from healthy individuals, and then correlated the findings with those of EPCs from type 2 DM patients with and without CAD. Materials and Methods: EPCs from 15 healthy and 55 patients were exposed to HG, OxLDL, or both before evaluating EPC count, migration and NO production, and expression of CXCR4 and members of Pi3K/Akt/eNOS signaling cascade. Results: Counts, migration, CXCR4 expression, and NO production were significantly reduced in EPCs from DM and CAD patients compared with that obtained in EPCs from healthy, and were further reduced in DM patients with CAD. The expression of CXCR4 and activation of Pi3K/Akt/eNOS signaling cascade were suppressed in OxLDL-and HG-treated EPCs, and this suppression was exacerbated when EPCs were treated simultaneously with HG and OxLDL. Conclusions: Hyperglycemia and elevated circulating OxLDL in DM patients with CAD severely impair EPC migration. These results suggest that the underlying mechanism for this impaired EPC migration is linked to the CXCR4/Pi3K/Akt/eNOS signaling pathway. (C) 2010 Elsevier Ltd. All rights reserved.
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