脂蛋白(a)对巨噬细胞清道夫受体-A表达的影响

Lipoprotein(a) increases acetylated low density lipoprotein uptake through up-regulation of scavenger receptor class A type I and type II in THP-1 derived macrophages

目的 研究脂蛋白 (a) [lipoprotein(a) ,Lp(a) ]对巨噬细胞清道夫受体A(scavengerreceptorclassAtypeIandtypeII,ScR A)的影响。方法 利用细胞培养、受体摄取配体及Northern印迹杂交方法 ,观察Lp(a)对从人类单核细胞株细胞形成的巨噬细胞受体摄取乙酰化LDL (acetylatedLDL ,Ac LDL)以及对THP 1细胞形成的巨噬细胞ScR AmRNA表达的影响。结果 人类单核细胞株细胞形成的巨噬细胞对Ac LDL的结合量随Lp(a)浓度的增加而增加 ,而天然LDL对此无影响。加入 5 0μg/mlLp(a) ,巨噬细胞对Ac LDL结合量为 ( 188 0 6± 16 80 )ng/mg蛋白 ,与对照组的 ( 4 8 2 6± 5 61)ng/mg蛋白比较显著增加 (P <0 0 1) ;巨噬细胞对Ac LDL的摄入量为 ( 3 63 80± 11 77)ng/mg蛋白 ,与对照组的 ( 2 2 8 15± 17 0 7)ng/mg蛋白比较显著增加 (P <0 0 5 ) ;巨噬细胞对Ac LDL的降解量为( 94 8 17± 3 1 43 )ng/mg蛋白与对照组的 ( 60 8 68± 3 8 11)ng/mg蛋白比较显著增加 (P <0 0 5 )。加入5 0 μg/mlLp(a) ,其ScR AmRNA表达明显增强 ,与对照组比较增强 4 3 5 6%。 结论 Lp(a)可增强从THP 1细胞形成的巨噬细胞ScR A基因的表达 ,Lp(a)的这种作用可能参与了动脉粥样硬化形成和发展的病理过程。

Objective To investigate whether lipoprotein(a) can influence macrophage scavenger receptor class A type I and type II (ScR-A). Methods After treatment of 12-O-tetradecanoylphobol-13-acetate differentiated THP-1 macrophages with different concentration of Lp(a), the acetylated low density lipoprotein (Ac-LDL) uptakes by scavenger receptor (including 4℃ binding, 37℃ association and 37℃ degradation) and ScR-A mRNA expression were measured. Results Ac-LDL binding was increased in a concentration dependent manner by treatment of Lp(a) but not by native LDL. Compared with controls, Ac-LDL binding was markedly increased [(188.06±16.80) ng/mg protein vs (48.26±5.61) ng/mg protein ,P<0.01], Ac-LDL association was significantly increased [(363.80±11.77) ng/mg protein vs (228.15±17.07) ng/mg protein, P<0.05], Ac-LDL degradation was also significantly enhanced [(948.17±31.43) ng/mg protein vs (608.68±38.11) ng/mg protein, P<0.05]. The macrophage ScR-A mRNA expression was augmented by 43.56% with treatment of 50 μg/ml Lp(a) compared with controls. Conclusion It is suggested that Lp(a) could contribute to atherosclerotic formation and devolepment by increasing macrophage expression of ScR-A in THP-1 derived macrophages.