Upregulation of lectinlike oxidized low-density lipoprotein receptor-1 expression contributes to the vein graft atherosclerosis: modulation by losartan.
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.
Ge
Junbo
J
Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China, 180 Fenglin Road, Shanghai 200032, PR China. jbge@zshospital.net
Huang
Dong
D
Liang
Chun
C
Luo
Yukun
Y
Jia
Qingzhe
Q
Wang
Keqiang
K
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000601:surgery; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D004730:Endothelium, Vascular / Q000378:metabolism; D006965:Hyperplasia; D007150:Immunohistochemistry; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D011817:Rabbits; D011973:Receptors, LDL / Q000378:metabolism*; D051131:Receptors, Oxidized LDL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017539:Tunica Intima / Q000473:pathology; D015854:Up-Regulation; D014680:Veins / Q000637:transplantation*
D047228:Angiotensin II Type 1 Receptor Blockers; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D019808:Losartan