The exploration of the potential effects of high density lipoprotein on human endothelial progenitor cells

• Main Authors: Chun-Yao Huang, 黃群耀
• Other Authors: 徐國基
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/76336944830858926136

博士 === 臺北醫學大學 === 臨床醫學研究所 === 101 === Recent clinical evidence failed to demonstrate the benefits of elevation of serum high density lipoprotein (HDL), suggesting potential loss of protective effects of HDL at high concentrations. This study aimed to investigate the concentration-related effects of HDL on in vitro and in vivo function of human endothelial progenitor cells (EPCs) and related angiogenesis. Early and late-outgrowth EPCs were generated from human circulating mononuclear cells. Oxidized low density lipoprotein (oxLDL) reduced viability of late-outgrowth EPCs, which was reversed dose-dependently by HDL. In the absence of oxLDL, HDL at low concentrations (5-50μg/mL, equal to 0.5-5mg/dL in human) enhanced EPC tube formation by activating PI3K/Akt/eNOS pathways. Moderate to high concentrations (400-800μg/mL) of HDL paradoxically enhanced EPC senescence and impaired tube formation by activating Rho-associated kinase (ROCK) and inhibiting PI3K/Akt and p38 MAPK pathways. ROCK inhibitors, either Y27632 or statins, prevented high HDL-induced EPC senescence and improved in vitro tube formation as well as in vivo capacity of angiogenesis of EPCs. While protecting EPCs from the injury of oxLDL, moderate to high concentrations of HDL paradoxically impaired EPCs and related angiogenesis in the absence of oxLDL by activating ROCK pathways, providing mechanistic evidence of potential hazard effects of HDL.