AMPK activation reduces the number of atheromata macrophages in ApoE deficient mice

Jing Wang, Ang Ma, Ming Zhao, Haibo Zhu*

*Corresponding author for this work

Research output: Contribution to journalArticle

18 Scopus citations

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. In addition, AMPK activation induced a change in Ly6C expression by monocytes: from high to low. 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.

Original languageEnglish (US)
Pages (from-to)97-107
Number of pages11
JournalAtherosclerosis
Volume258
DOIs
StatePublished - Mar 1 2017

Keywords

  • AMPK
  • Atherosclerosis
  • Ccr2
  • Ly6C
  • Migration
  • Monocyte

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'AMPK activation reduces the number of atheromata macrophages in ApoE deficient mice'. Together they form a unique fingerprint.

  • Cite this