Oct 13, 2012

TLR4 antagonist reduces early-stage atherosclerosis in diabetic apolipoprotein E-deficient mice

The Journal of Endocrinology
Zhongyang LuYan Huang

Abstract

Although it has been reported that deficiency of toll-like receptor 4 (TLR4) is associated with reduced atherosclerosis in atherosclerosis-prone mice and attenuated pro-inflammatory state in diabetic mice, it remains undetermined whether treatment with a TLR4 antagonist reduces atherosclerosis in nondiabetic or diabetic mice that have TLR4 expression. In this study, we determined the effect of Rhodobacter sphaeroides lipopolysaccharide (Rs-LPS), an established TLR4 antagonist, on early-stage atherosclerosis in nondiabetic and streptozotocin-induced diabetic apolipoprotein E-deficient (Apoe(-/-)) mice. Analysis of atherosclerotic lesions of both en face aortas and cross sections of aortic roots showed that administration of Rs-LPS in 14-week-old diabetic Apoe(-/-) mice for 10 weeks significantly reduced atherosclerotic lesions. Although atherosclerotic lesions in nondiabetic Apoe(-/-) mice appeared to be decreased by Rs-LPS treatment, the difference was not statistically significant. Metabolic study showed that Rs-LPS significantly lowered serum levels of cholesterol and triglycerides in nondiabetic mice but not in diabetic mice. Furthermore, immunohistochemistry studies showed that Rs-LPS inhibited the expression of interleukin...Continue Reading

  • References23
  • Citations30

Mentioned in this Paper

Vascular Inflammations
Immunohistochemistry
TLR4 gene
Radionuclide Metabolic Studies
Plaque, Atherosclerotic
Toll-like receptor 4
Analgesics, Anti-Inflammatory
Proteins, Recombinant DNA
Antagonist Muscle Action
Atherogenesis

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