Ge Junbo, Huang Dong, Liang Chun, Luo Yukun, Jia Qingzhe, Wang Keqiang
Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China, 180 Fenglin Road, Shanghai 200032, PR China.
Atherosclerosis. 2004 Dec;177(2):263-8. doi: 10.1016/j.atherosclerosis.2004.07.021.
Vein grafts interposed to arteries are susceptible to the development of accelerated atherosclerosis. The role of lectinlike oxidized LDL (ox-LDL) receptor-1 (LOX-1) expression in the atherosclerotic lesions of vein grafts has not been clarified. The current study was designed to examine the expression of LOX-1 in vein grafts atherosclerosis and the modulating effect of losartan on it. Autologous external jugular veins were grafted to common carotid arteries in 30 male New Zealand White rabbits. After surgery, rabbits were fed with high cholesterol diet (HC), high cholesterol diet plus losartan (10 mg/kg/day, LHC) or regular chow (control, n = 10 in each group) for 12 weeks. LOX-1 expressions in the grafts were examined by immunohistochemistry, semi-quantitative RT-PCR and Western blot. Neointimal hyperplasia was observed in all vein grafts characterized by extensive intimal thickening. Atherosclerotic lesions were found in vein grafts of HC group, which were attenuated by losartan. Losartan also reduced the vein grafts atherosclerotic plaque vulnerability. LOX-1 expression was low in the endothelium and neointima of vein grafts in control group and was significantly increased in the endothelium and atherosclerotic lesions in HC group but not in LHC group. In conclusion, LOX-1 was expressed in endothelium and neointima of autologous vein grafts of rabbits. Increased LOX-1 expression was associated with vein grafts atherosclerosis development. Downregulation of LOX-1 by losartan might contribute to its attenuating effect on vein grafts atherosclerosis.
植入动脉的静脉移植物易发生加速动脉粥样硬化。凝集素样氧化低密度脂蛋白（ox-LDL）受体-1（LOX-1）表达在静脉移植物动脉粥样硬化病变中的作用尚未阐明。本研究旨在检测LOX-1在静脉移植物动脉粥样硬化中的表达以及氯沙坦对其的调节作用。将30只雄性新西兰白兔的自体颈外静脉移植到颈总动脉。术后，兔子分别给予高胆固醇饮食（HC）、高胆固醇饮食加氯沙坦（10 mg/kg/天，LHC）或常规饲料（对照组，每组n = 10），持续12周。通过免疫组织化学、半定量逆转录-聚合酶链反应（RT-PCR）和蛋白质免疫印迹法检测移植物中LOX-1的表达情况。在所有静脉移植物中均观察到内膜增生，其特征为内膜广泛增厚。在HC组的静脉移植物中发现了动脉粥样硬化病变，而氯沙坦可使其减轻。氯沙坦还降低了静脉移植物动脉粥样硬化斑块的易损性。对照组静脉移植物的内皮和内膜中LOX-1表达较低，HC组的内皮和动脉粥样硬化病变中LOX-1表达显著增加，而LHC组则未增加。综上所述，LOX-1在兔自体静脉移植物的内皮和内膜中表达。LOX-1表达增加与静脉移植物动脉粥样硬化的发展相关。氯沙坦下调LOX-1可能有助于其减轻静脉移植物动脉粥样硬化的作用。
