Adenosine receptor A2a deficiency in leukocytes increases arterial neointima formation in apolipoprotein E-deficient mice

Huan Wang, Weiyu Zhang, Rong Tang, Chuhong Zhu, Christoph Bucher, Bruce R. Blazar, Jian Guo Geng, Chunxiang Zhang, Joel Linden, Chaodong Wu, Yuqing Huo

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16 Scopus citations

Abstract

Objective-: To use the mice deficient in both adenosine receptor A2A (A2AR) and apolipoprotein E (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.Methods and results-: In apoE mice, A2AR deficiency increased the size of the arterial neointima in injured carotid arteries by 83%. Arterial neointima formation was also enhanced in chimeric mice that underwent bone marrow transplantation (these mice lacked A2AR in their bone marrow-derived cells). Epifluorescence intravital microscopy showed that neutrophil rolling and adherence to the injured arterial area were 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, P-selectin glycoprotein ligand-1 (PSGL-1) clustering, and the affinity of b2 integrins. The inhibition of p38 phosphorylation abrogated the increased PSGL-1 clustering and β2 integrin affinity, thus reversing the increased homing ability of A2AR-deficient leukocytes. Conclusion-: A2AR plays a complex role in inflammation and tissue injury. The deficiency of A2AR enhances the homing ability of leukocytes and increases the formation of the arterial neointima after injury. A2AR antagonists are being tested for the treatment of neurodegenerative and other chronic diseases. An evaluation of the effect of A2AR antagonists on arterial restenosis after arterial angioplasty should be conducted.

Original languageEnglish (US)
Pages (from-to)915-922
Number of pages8
JournalArteriosclerosis, thrombosis, and vascular biology
Volume30
Issue number5
DOIs
StatePublished - May 1 2010

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Keywords

  • Adhesion molecules
  • Atherosclerosis
  • Carotid arteries
  • Leukocytes
  • Restenosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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