南方医科大学学报 ›› 2004, Vol. 24 ›› Issue (09): 980-983.

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血管内皮细胞中ABCA1的表达及其在动脉粥样硬化发生中的意义

李建华, 郭志刚, 吴平生, 杨永红, 赖文岩   

  1. 第一军医大学南方医院心内科, 广东, 广州, 510515
  • 出版日期:2004-09-20 发布日期:2004-09-20
  • 基金资助:
    收稿日期:2003-10-11。
    基金项目:国家自然科学基金(30171028);广东省自然科学基金(010616)
    作者简介:李建华(1971-),女,1995年毕业于第四军医大学,现为第一军医大学在读博士研究生,主治医师、讲师,电话:020-61365725,E-mail:lijhlijh@126.com
    通讯作者:郭志刚,电话:020-61641515

Expression of ABCA1 in vascular endothelial cells and its significance in the pathogenesis of atherosclerosis

LI Jian-hua, GUO Zhi-gang, WU Ping-sheng, YANG Yong-hong, LAI Wen-yan   

  1. 第一军医大学南方医院心内科, 广东, 广州, 510515
  • Online:2004-09-20 Published:2004-09-20

摘要: 目的 以人的血管内皮细胞ECV304为靶点,研究Ox-LDL和8-Br-cAMP对ATP-结合盒转运子A1(ABCA1)、细胞间粘附因子-1(ICAM-1)及单核细胞趋化因子-1(MCP-1)基因mRNA和蛋白质表达的影响,阐明ABCA1基因在动脉粥样硬化(AS)形成中的可能机制。方法 复苏培养血管内皮细胞,无血清培养基培养静止12 h后,分别加入Ox-LDL (30 ng/ml)、8-Br-cAMP (0.5 mmol/L)刺激3、6、12、24 h,设未加刺激同时孵育24 h的细胞为阴性对照组,以RT-PCR和Western蛋白印迹法检测ABCA1、ICAM-1及MCP-1 mRNA和蛋白质表达量。结果 血管内皮细胞ECV304在给予Ox-LDL刺激后,ABCA1、ICAM-1、MCP-1的mRNA和蛋白质水平均增高,ICAM-1的高峰时间在12 h,其余高峰时间在6 h;在8-Br-cAMP的刺激下,ABCA1、ICAM-1、MCP-1的mRNA和蛋白质水平也增高,高峰时间均在6 h。结论 公认的致AS因素Ox-LDL可通过引起血管内皮细胞ECV304中炎性细胞因子ICAM-1、MCP-1 mRNA及蛋白质水平增加,参与AS的形成,同时抗AS基因ABCA1在Ox-LDL刺激下代偿增加,具有AS保护作用。cAMP不仅可增加ABCA1的表达,而且可增加ICAM-1、MCP-1表达。

Abstract: Objective To investigate the changes in the expressions of ATP-binding cassette transporter A1 (ABCA1), intercellular cell adhesion molecule type 1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) at mRNA and protein levels after the treatment of the vascular endothelial ECV304 cells with oxidized low-density lipoprotein (Ox-LDL) and 8-Br-cAMP, thereby to explore possible mechanisms by which ABCA1 affects the formation of atherosclerosis (AS). Methods Resuscitated and cultured ECV304 cells were incubated in serum-free medium for 12 h to induce the quiescence phase of growth, which were subsequently treated with Ox-LDL (30 ng/ml) and 8-Br-cAMP (0.5 mmol/L) respectively for 3, 6, 12, and 24 h. After the cells were harvested at the specified time points, the mRNA and protein levels of ABCA1, ICAM-1 and MCP-1 were detected by RT-PCR and Western blotting, respectively. Results The mRNA and protein expression levels of ABCA1, ICAM-1 and MCP-1 all increased after treatments with Ox-LDL and 8-Br-cAMP. The highest expression of ICAM-1 occurred in cells with a 12-hour treatment, and those of ABCA1 and MCP-1 occurred following 6-hour incubation with Ox-LDL. The expression peaks of ABCA1, ICAM-1 and MCP-1 all took place after 6-hour incubation with 8-Br-cAMP. Conclusions The mRNA and protein expressions of ICAM-1 and MCP-1 in vascular endothelial ECV304 cells increase in response to Ox-LDL treatment, in the event of which ABCA1 is also up-regulated to offer protective effects against AS. cAMP not only enhances the expression of ABCA1 but also those of ICAM-1 and MCP-1.

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