ABCA1-565C/T基因多态性对心梗患者来源的巨噬细胞胆固醇外流功能影响及其机制研究

Effect of ABCA1-565CT Variation on HDL-induced Cholesterol Efflux in Myocardial Infarction Patients

目的比较三磷酸腺苷结合盒转运子A1(ABCA1)启动子区-565C/T不同基因型的心肌梗死患者巨噬细胞胆固醇外流功能及ABCA1蛋白表达。方法应用人外周血单核细胞原代细胞培养及乙酰化低密度脂蛋白(Ac-LDL)诱导获得巨噬细胞,3H标记的胆固醇测量巨噬泡沫细胞胆固醇外流功能;采用western blot技术测量ABCA1蛋白表达。结果(1)单核细胞原代培养分化成巨噬细胞,经Ac-LDL诱导成泡沫细胞;(2)ABCA1-565C/TTT型巨噬泡沫细胞胆固醇流出率低于CT型和CC型;(3)TT型巨噬细胞中ABCA1蛋白表达显著低于CT型和CC型,差异有统计学意义(P<0.05)。结论ABCA1-565C/T位点TT基因型ABCA1的蛋白表达及胆固醇外流功能较CC、CT型减低,推测TT基因型通过影响ABCA1蛋白表达而影响巨噬细胞胆固醇外流功能而促进冠心病的发生和发展。

Objective To compare the cholesterol effluxes and ATP - binding cassette transporter 1 （ ABCA1 ） protein expressions in macrophages of myocardial infarction patients with different promoter - -565 C/T genotypes. Methods The macrophages were obtained by cultivation of human peripheral primary monoeytes and acetyl - LDL inducement. The cholesterol efflux was measured by 3 H label, and ABCA1 protein expression was assayed by Western blot technique. Results （ 1 ） The primary monocytes were cultivated to become macrophages, which were induced by Ac - LDL to become foam cells. （ 2 ） The cholesterol efflux rate from foam macrophages of ABCAI - 565C/T TT type was lower than that from CT and CC type. （ 3 ） ABCA1 expression in TT typed cells was obviously lower than in CT and CC typed cells （P 〈 0. 05 ）. Conclusion The ABCA1 protein expression and cholesterol efflux in ABCAI -565 C/T site TT genotype are lower than those in CC and CT genotype. The result suggests that TT genotype may influence the macrophage cholesterol efflux by inhibiting the ABCA1 expression so as to promote the occurrence and development of coronary heart disease.