ApolipoproteinA Impairs Endothelial Progenitor Cell-mediated Vasculogenesis and Its Mechanism

作者:Wang Ren; Zhang Kai; Li Shuang; Tong Zhong-Yo; Li Guo-Hua; Zhao Zhan-Zhi; Lin Xiao-Long; Zhao Yue; Liu Feng-Tao; Wang Zuo*; Jiang Zhi-Sheng
来源:Progress in Biochemistry and Biophysics, 2013, 40(8): 757-765.
DOI:10.3724/SP.J.1206.2012.00561

摘要

Improvement of blood flow and promotion of neovascularization are important therapeutic measures for ischemic peripheral vascular diseases. Since apolipoproteinA(ApoA) is a glycoprotein with repetitive kringle domains exhibiting 75% to 98% structural homology with plasminogen(Plg), ApoA may also have a negative effect on endothelial progenitor cell (EPC)-induced vasculogenesis through Plg-like inhibitory effects on EPC proliferation, adhesion, migration and vasculogenesis. To evaluate the effect of ApoA on EPCs-induced vasculogenesis. ApoA was stably expressed and prepared from COS-7 cell line which were transfected with the expression plasmids pSG-5 encoding human ApoA cDNA, then purified by immunoaffinity chromatography; EPCs were isolated from the bone marrow of ApoA transgenic mice, wild-type litter mates and normal mice. These cells were cultured without or with ApoA before transplantation. Hindlimb ischemia models were surgically induced in mice, which then received an intravenously injection of 3 x 10(5) EPCs. At 3, 7 and 14 days post EPC transplantation, the adhesion, migration abilities and capillary density in calf muscles were assessed. Results indicate that ApoA significantly reduced the adhesion and migration abilities of EPCs. Furthermore, the tubule-like formation of EPCs on Matrigel gels was damaged. In, vivo experiments showed the number of EPCs home to ischemic peripheral vascular, and the number of capillary vessels decreased significantly in ApoA transgenic mice. This study demonstrated that ApoA could attenuate the adhesion, migration, and homing abilities of EPCs and could impair the vasculogenesis ability of EPCs.

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