Lack of Toll-like receptor 4 or myeloid differentiation factor 88 reduces atherosclerosis and alters plaque phenotype in mice deficient in apolipoprotein E.

ABSTRACT: Toll-like receptors (TLRs) and the downstream adaptor molecule myeloid differentiation factor 88 (MyD88) play an essential role in the innate immune responses. Here, we demonstrate that genetic deficiency of TLR4 or MyD88 is associated with a significant reduction of aortic plaque areas in atherosclerosis-prone apolipoprotein E-deficient mice, despite persistent hypercholesterolemia, implying an important role for the innate immune system in atherogenesis. Apolipoprotein E-deficient mice that also lacked TLR4 or MyD88 demonstrated reduced aortic atherosclerosis that was associated with reductions in circulating levels of proinflammatory cytokines IL-12 or monocyte chemoattractant protein 1, plaque lipid content, numbers of macrophage, and cyclooxygenase 2 immunoreactivity in their plaques.

SUBMITTER: Michelsen KS 

PROVIDER: S-EPMC489994 | biostudies-literature | 2004 Jul

REPOSITORIES: biostudies-literature