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


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.
Wang
Huan
H
Department of Medicine, University of Minnesota, Minneapolis, MN 55455, USA.
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
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000276:immunology / Q000503:physiopathology*; D005260:Female; D005487:Foam Cells / Q000473:pathology / Q000502:physiology; D007249:Inflammation / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D043705:Receptor, Adenosine A2A / Q000172:deficiency / Q000502:physiology*; D018183:Transplantation Chimera
D001057:Apolipoproteins E; D043705:Receptor, Adenosine A2A