Inactivation of the adenosine A2A receptor protects apolipoprotein E-deficient mice from atherosclerosis. Academic Article uri icon

abstract

  • 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.

published proceedings

  • Arterioscler Thromb Vasc Biol

author list (cited authors)

  • Wang, H., Zhang, W., Zhu, C., Bucher, C., Blazar, B. R., Zhang, C., ... Huo, Y.

citation count

  • 54

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

publication date

  • July 2009