TLR4 antagonist inhibits atherogenesis

Early epidemiological studies have shown an association between infection with gram-negative bacteria and atherosclerosis. In recent years, animal studies in atherosclerosis-prone mice have provided strong evidence that TLR4 plays an important role in atherosclerosis. It has been demonstrated that deficiency of TLR4 or MyD88 in apolipoprotein E-deficient (Apoe−/−) mice is associated with a significant reduction of atherosclerosis.

Lu et al. conducted a study to determine the effect of R. sphaeroides lipopolysaccharide (Rs-LPS), an established TLR4 antagonist, on the early-stage atherosclerosis in non-diabetic and diabetic Apoe-/- mice. Analysis of atherosclerotic lesions in 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 atherosclerosis while metabolic experiments showed that Rs-LPS significantly lowered serum levels of cholesterol and triglycerides in non-diabetic mice. This study demonstrated for the first time that TLR4 antagonist Rs-LPS inhibited early stage atherosclerosis in diabetic Apoe-/- mice. Lu et al. (2013) Journal of Endocrinology 216, 61-71.

Read the full article at DOI: 10.1530/JOE-12-0338.