Inactivation of the adenosine A2A receptor protects apolipoprotein E-deficient mice from atherosclerosis.
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BACKGROUND: Atherosclerosis is a chronic inflammatory disease of the arterial vessel wall. The A(2A) receptor (A(2A)R) plays a central role in many antiinflammatory effects of adenosine. However, the role of A(2A)R in atherosclerosis is not clear. METHODS AND RESULTS: The knockout of A(2A)R in apolipoprotein E-deficient (Apoe(-/-)/A(2A)R(-/-)) 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(-/-)/A(2A)R(-/-) mice developed smaller lesions, as did chimeric Apoe(-/-) mice lacking A(2A)R in bone marrow-derived cells (BMDCs). The lesions of those mice exhibited a low density of foam cells and the homing ability of A(2A)R-deficient monocytes did not change. Increased foam cell apoptosis was detected in atherosclerotic lesions of Apoe(-/-)/A(2A)R(-/-) mice. In the absence of A(2A)R, macrophages incubated with oxidized LDL or in vivo-formed foam cells also exhibited increased apoptosis. A(2A)R 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 A(2A)R-deficient foam cells. CONCLUSIONS: Inactivation of A(2A)R, especially in BMDCs, inhibits the formation of atherosclerotic leisons, suggesting that A(2A)R inactivation may be useful for the treatment of atherosclerosis.
Arterioscler Thromb Vasc Biol
author list (cited authors)
Wang, H., Zhang, W., Zhu, C., Bucher, C., Blazar, B. R., Zhang, C., ... Huo, Y.
complete list of authors
Wang, Huan||Zhang, Weiyu||Zhu, Chuhong||Bucher, Christoph||Blazar, Bruce R||Zhang, Chunxiang||Chen, Jiang-Fan||Linden, Joel||Wu, Chaodong||Huo, Yuqing