| Objective Hyperhomocysteinemia has been identified as a new independent risk factor for atherosclerosis in resent years. Up to now, the mechanism of homocysteine in atherosclerosis is not clear. Endothelial dysfunction plays a pivotal role in the initial stage of atherosclerosis. Homocysteine can induce endothelial dysfunction through a few kinds of mechanisms including:damage of endothelial barrier function, induced apoptosis in endothelial cells, upregulation of adhesion molecules in endothelium, inhibition of nitric oxide, and so on. Oxidized low density lipoprotein (oxLDL) play a key role in the pathogenesis of endothelial dysfunction and atherosclerosis. Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) is a major specific receptor for oxLDL in endothelial cells. Its inducible expression is involved in oxLDL mediated multiple roles in atherogenesis. Folic acid has close relations with the metabolism of homocysteine. Insufficient intake of folic acid causes hyperhomocysteinemia. Folic acid can also ameliorate endothelial function, decrease the risk of cardiovascular diseases. Statins are the specific 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. These agents, besides lowering total and LDL cholesterol, have a multitude of other effects independent of lipid-lowering effect including improvement of endothelial function, which may have a bearing on the cardioprotective effects. In the present experimental study, we examined the expression of LOX-1 mRNA in human umbilical vein endothelial cells (HUVECs) to investigate the possible molecular mechanism of homocysteine in atherogenesis.Methods All of 16 groups were divided randomly at different concentration of Hcy and folic acid or of Hcy and fluvastatin. HUVECs isolated from fresh umbilical cord were incubated with different concentration of Hcy or/andfluvastatin, folic acid for 24 hours. Total RNA was extracted with TRIzol reagent. Semi-quantitative reverse transcription-polymerase chain reaction was performed to quantify the mRNA expression of LOX-1 gene in HUVECs. Results (1) Hey of physical concentration increased the expression of LOX-1 mRNA compared with control group, but there was no significant difference. The LOX-1 mRNA expression of HUVECs incubated with pathphysical concentration of Hey was increased , compared with control group. But only difference between lOOumol/L Hey and control group was so remarkable to reach signifenence(P<0.05), (2) Pretreatment of folic acid increased the expression of LOX-1 mRNA compared with control group, nevertheless it was no significant difference. Compared with Hey only, coincubation with Hey and folic acid attenuated the expression of LOX-1 mRNA . The difference was of no signiference. There was no significant difference between coincubation with Hey and folic acid and control group. (3) Compared with control group, the LOX-1 mRNA expression of HUVECs incubated with Hey and fluvastatin was enhanced, but it didn't reach the significance. Coincubation with Hey and fluvastatin decreased the expression of LOX-1 mRNA, however there was no remarkable difference compared with incubation with Hey only. The difference of the expression of LOX-1 mRNA between control group and coincubation with Hey and fluvastatin was no significant.Conclusions (1) Homocysteine can upregulate mRNA expression of LOX-1 in human umbilical vein endothelial cells. It's suggested that lectin-like oxidized low density lipoprotein receptor-1 may mediate the effect of homocysteine in atherosclerosis. (2) Folic acid has a tendency to downregulate enhanced mRNA expression of LOX-1 induced by homocysteine in human umbilica vein endothelial cells. Folic acid represents it's beneficial effect through antagonizing homocysteine. (3) Fluvastatin has a tendency to downregulate augmented mRNAexpression of LOX-1 induced by homocysteine in human umbilica vein endothelial cells. The reduced expression of LOX- imRNA by fluvastatin may be involved in its multiple beneficial effects independent of lipid-lowering effect.
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