Department of Pathology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, #5, Dong Dan San Tiao, Beijing 100005, China.
Exp Biol Med (Maywood). 2010 Sep;235(9):1082-92. doi: 10.1258/ebm.2010.010060. Epub 2010 Aug 19.
High-density lipoprotein (HDL) is known as an important factor in vascular wall remodeling that also affects gene expression in cell proliferation and differentiation. In this article, the role of HDL on endothelial progenitor cell (EPC) proliferation, angiogenesis and the signal pathway involved was studied, particularly the influence of HDL in strengthening the promoting effect of EPCs on wound healing of the arterial wall in hypercholesterolemic rats. Mononuclear cells isolated from rat bone marrow displayed characteristics of EPCs after cultivation. The role of HDL on EPC function and the signal pathway involved were studied by Western blotting, in vitro migration and 'tube' formation. Re-endothelialization and the number of circulating EPCs were compared between normal rats, hypercholesterolemic rats and hypercholesterolemic rats with HDL treatment. Results showed that HDL participated in the healing process by promoting EPC proliferation, migration and 'tube' formation. HDL activates cyclin D1 via phosphatidylinositol 3-kinase (PI3K)/Akt stimulation. Inhibition of PI3K/Akt via pharmacological or small interfering RNA approaches significantly attenuated HDL-induced EPC migration, proliferation and 'tube' formation. Results of experiments in vivo showed that HDL increased the number of circulating EPCs and promoted re-endothelialization in wound healing. These findings demonstrate for the first time that PI3K/Akt-dependent cyclin D1 activation plays an essential role in HDL-induced EPC proliferation, migration and angiogenesis.
高密度脂蛋白（HDL）是血管壁重构的重要因素，也影响细胞增殖和分化过程中的基因表达。本文研究了 HDL 对内皮祖细胞（EPC）增殖、血管生成及相关信号通路的作用，特别是研究了 HDL 如何增强 EPC 在高胆固醇血症大鼠动脉壁损伤愈合中的促进作用。从大鼠骨髓中分离出的单核细胞在培养后表现出 EPC 的特征。通过 Western blot、体外迁移和“管”形成实验研究了 HDL 对 EPC 功能及其相关信号通路的作用。比较了正常大鼠、高胆固醇血症大鼠和给予 HDL 治疗的高胆固醇血症大鼠之间的再内皮化和循环 EPC 数量。结果表明，HDL 通过促进 EPC 增殖、迁移和“管”形成参与愈合过程。HDL 通过磷酸肌醇 3-激酶（PI3K）/Akt 刺激激活细胞周期蛋白 D1。通过药理学或小干扰 RNA 方法抑制 PI3K/Akt，可显著减弱 HDL 诱导的 EPC 迁移、增殖和“管”形成。体内实验结果表明，HDL 增加了循环 EPC 的数量，并促进了伤口愈合中的再内皮化。这些发现首次表明，PI3K/Akt 依赖性细胞周期蛋白 D1 激活在 HDL 诱导的 EPC 增殖、迁移和血管生成中起关键作用。
