oxidized cholesterol exacerbates toll-like receptor 4 expression and activity in the hearts of rats with myocardial infarction

Introduction: the present study examined the effects of high cholesterol and high oxidized-cholesterol diets on the myocardial expression of tlr4 and pro-inflammatory cytokine in rats. methods: male wistar rats were allocated into 6 groups and fed with a normal diet, cholesterol, and oxidized-cholesterol rich diets with or without isoproterenol-induced myocardial infarction. tlr4 and myd 88 expression and levels tumor necrosis factor alpha (tnf-α) and interleukin 6 (il-6) were measured in the heart and serum. results: oxidized cholesterol-fed animals had higher serum levels of oxidized low-density lipoprotein (ldl) (263 ± 13 ng/dl) than the cholesterol-fed animals (98 ± 8 ng/dl; p < 0.001). a high level of oxidized-ldl caused fibrotic cell formation and enhanced neutrophil infiltration in the absence of mi. both cholesterol and oxidized-cholesterol upregulated tlr4 mrna expression and increased tnf-α and il-6 production in the hearts of rats with mi. in rats fed with oxidized-cholesterol the serum and myocardial levels of tnf-α (653 ± 42 pg/ml, 1375 ± 121 pg/100 mg, respectively) were higher than mi group (358±24 pg/ml, p < 0.001 and 885 ± 56 pg/100 mg, p < 0.01). a significant correlation was seen between tlr4 expression and infarct size. conclusion: these findings suggest that cardiac tlr4 is preferentially upregulated by oxidized cholesterol in rats. oxidized cholesterol may have a critical role in cardiac toxicity in the absence of pathological conditions.