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


ABSTRACT: 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.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.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.

SUBMITTER: Wang H 

PROVIDER: S-EPMC2724834 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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

Wang Huan H   Zhang Weiyu W   Zhu Chuhong C   Bucher Christoph C   Blazar Bruce R BR   Zhang Chunxiang C   Chen Jiang-Fan JF   Linden Joel J   Wu Chaodong C   Huo Yuqing Y  

Arteriosclerosis, thrombosis, and vascular biology 20090430 7


<h4>Background</h4>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.<h4>Methods and results</h4>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 a  ...[more]

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