Abstract
OBJECTIVE: To investigate the effect of atorvastatin on the expression of lectin- like oxLDL receptor 1 (LOX-1) and endothelial nitric oxide synthase (eNOS) in collateral vessels of hypercholesterolemic rats. METHODS: Forty male SD rats were randomized equally into 4 groups: femoral ligation group (L), hypercholesterolemia + femoral ligation group (HL), hypercholesterolemia+atorvastatin+femoral ligation group (AL), and hypercholesterolemia+normal saline+femoral ligation group (NL). The rats in the latter 3 groups were fed atherogenic diet for 8 weeks. At the end of the 8 weeks, the rats were subjected to femoral artery ligation with or without intraperitoneal injection of atorvastatin (AL group) or saline (NL group). Two weeks later, all the rats were euthanized and the expressions of LOX-1 and eNOS in the collateral vessels were detected with immunofluorescence assay. In the in vitro experiment, cultured human umbilical vein endothelial cells (HUVECs) were transfected with LOX-1 siRNA followed by treatment with oxLDL and/or atorvastatin. The expressions of LOX-1 and eNOS in the cells were detected with realtime PCR and Western blotting, and the cellular NO production was examined with Griess assay. RESULTS: The collateral vessels of rats with normal feeding expressed LOX-1, which was significantly increased in the collateral vessels of hypercholesterolemic rats; atorvastatin treatment significantly lowered LOX-1 expressions in the hypercholesterolemic rats. In normally fed rats, the growing collateral vessels exhibited strong eNOS expressions, which were lowered in hypercholesterolemic rats and enhanced after atorvastatin treatment. In the cell experiment, HUVECs with oxLDL treatment showed a high LOX-1 expression and a low eNOS expression, and atorvastatin treatment of the cells down-regulated LOX-1 and up-regulated eNOS expressions. Inhibition of LOX-1 mediated by a specific LOX-1 siRNA abolished the effect of oxLDL stimulation on eNOS expression in the cells. CONCLUSION: Both hypercholesterolemia and oxLDL can induce endothelial dysfunction and impair collateral vessel growth via the LOX-1/eNOS pathway in rats, and atorvastatin treatment can restore the LOX-1/eNOS pathway to promote the growth of the collateral vessels, suggesting the potential of atorvastatin as a therapeutic agent to promote repair of collateral vessel injuries in ischemic diseases.