Adenosine receptor A2A deficiency in leukocytes increases arterial neointima formation in apolipoprotein E-deficient mice.
Adenosine receptor A2A deficiency in leukocytes increases arterial neointima formation in apolipoprotein E-deficient mice.
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DOI：
10.1161/atvbaha.109.202572
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发表时间：
2010-05
期刊：
影响因子：
--
通讯作者：
Huo Y
中科院分区：
文献类型：
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作者：
Wang H;Zhang W;Tang R;Zhu C;Bucher C;Blazar BR;Geng JG;Zhang C;Linden J;Wu C;Huo Y
The A2A receptor (A2AR) plays a complex role in inflammation and tissue injury. In this study, we used the mice deficient in both A2AR and apolipoprotein E (A2AR−/−/apoE−/−) to investigate the role of A2AR in mediating the interactions of leukocytes with injured arterial walls and the formation of arterial neointima induced by a guide wire. In apoE−/− mice, A2AR deficiency increased the size of arterial neointima in injured carotid arteries by 83%. Arterial neointima formation was also enhanced in bone marrow transplanted chimeric mice that lacked A2AR in their bone marrow-derived cells. Epifluorescence intravital microscopy showed that neutrophil rolling and adherence to the injured arterial area was enhanced by 80% and 110% in A2AR−/−/apoE−/− mice, respectively. This phenomenon occurred even though the protein levels of homing molecules on A2AR-deficient neutrophils were unchanged from those of wild type neutrophils. A2AR-deficient neutrophils exhibited an increase in the phosphorylation of p38 mitogen-activated protein kinase (MAPK), PSGL-1 clustering, and the affinity of b2 integrins. Inhibition of p38 phosphorylation abrogated the increased PSGL-1 clustering and b2 integrin affinity, thereby reversing the increased homing ability of A2AR-deficient leukocytes. The deficiency of A2AR enhances the homing ability of leukocytes and increases the formation of arterial neointima after injury. A2AR antagonists are being tested for the treatment of neurodegenerative diseases and other chronic diseases. Our results suggest that an evaluation of the effect of A2AR antagonists on arterial restenosis following arterial angioplasty should be conducted.
