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Title: AMPK activation reduces the number of atheromata macrophages in ApoE deficient mice. Author: Wang J, Ma A, Zhao M, Zhu H. Journal: Atherosclerosis; 2017 Mar; 258():97-107. PubMed ID: 28235712. Abstract: BACKGROUND AND AIMS: CC chemokine receptor 2 (Ccr2) governs migration of inflammatory Ly6Chi monocytes from the bone marrow (BM) to the circulating blood, which is a key step for macrophage accumulation during progression of atherosclerosis. Hyperlipidemia is often accompanied by low AMP-activated kinase (AMPK) activity and increased expression of Ccr2. The aim of this study was to examine whether there is a link between AMPK and chemokine networks. METHODS: ApoE-/- mice were fed a western diet and treated daily with AMPK activators (AICAR, A769662, or Metformin) or vehicle for 10 weeks. The effect of AMPK activators on pro-inflammatory myeloid cell numbers within the BM, blood, spleen, and aorta of ApoE-/- mice was then examined. RESULTS: We found that AMPK activation significantly reduced the number of Ly6Chi monocytes in the blood and atherosclerotic plaques. This reduction was caused by down-regulation of Ccr2 protein expression, which inhibited Ccr2-mediated migration of Ly6Chi monocytes from the BM to the circulation. There was no effect on proliferation or apoptosis of BM-derived Ly6Chi monocytes. AMPK activation caused Ly6Chi monocytes to accumulate in the BM, with a concomitant reduction in numbers in the blood and spleen. CONCLUSIONS: AMPK activation reduces the formation of atheromata-inducing macrophages in ApoE-/--deficient mice by inhibiting expression of Ccr2, thereby preventing the Ccr2-mediated migration of Ly6Chi monocytes from the BM. Therefore, AMPK may be a promising target for the treatment of atherosclerosis.[Abstract] [Full Text] [Related] [New Search]