| First Author | Wang H | Year | 2009 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 29 |
| Issue | 7 | Pages | 1046-52 |
| PubMed ID | 19407243 | Mgi Jnum | J:167816 |
| Mgi Id | MGI:4880635 | Doi | 10.1161/ATVBAHA.109.188839 |
| Citation | Wang H, et al. (2009) Inactivation of the adenosine A2A receptor protects apolipoprotein E-deficient mice from atherosclerosis. Arterioscler Thromb Vasc Biol 29(7):1046-52 |
| abstractText | 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. |
