Inactivation of the adenosine A2A receptor protects apolipoprotein E-deficient mice from atherosclerosis

Huan Wang, Weiyu Zhang, Chuhong Zhu, Christoph Bucher, Bruce R. Blazar, Chunxiang Zhang, Jiang Fan Chen, Joel Linden, Chaodong Wu, Yuqing Huo

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

BACKGROUND - Atherosclerosis is a chronic inflammatory disease of the arterial vessel wall. The A2A receptor (A2AR) plays a central role in many antiinflammatory effects of adenosine. However, the role of A2AR in atherosclerosis is not clear. METHODS AND RESULTS - The knockout of A2AR in apolipoprotein E-deficient (Apoe/A2AR) mice led to an increase in body weight and levels of blood cholesterol and proinflammatory cytokines, as well as the inflammation status of atherosclerotic lesions. Unexpectedly, Apoe/A2AR mice developed smaller lesions, as did chimeric Apoe mice lacking A2AR in bone marrow-derived cells (BMDCs). The lesions of those mice exhibited a low density of foam cells and the homing ability of A2AR-deficient monocytes did not change. Increased foam cell apoptosis was detected in atherosclerotic lesions of Apoe/A2AR mice. In the absence of A2AR, macrophages incubated with oxidized LDL or in vivo-formed foam cells also exhibited increased apoptosis. A2AR deficiency in foam cells resulted in an increase in p38 mitogen-activated protein kinase (MAPK) activity. Inhibition of p38 phosphorylation abrogated the increased apoptosis of A2AR-deficient foam cells. CONCLUSION - Inactivation of A2AR, especially in BMDCs, inhibits the formation of atherosclerotic leisons, suggesting that A2AR inactivation may be useful for the treatment of atherosclerosis.

Original languageEnglish (US)
Pages (from-to)1046-1052
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume29
Issue number7
DOIs
StatePublished - Jul 1 2009
Externally publishedYes

Keywords

  • Adenosine receptor
  • Apoptosis
  • Atherosclerosis
  • Macrophages

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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