Adenosine A2B Receptor Agonism Inhibits Neointimal Lesion Development After Arterial Injury in Apolipoprotein E–Deficient Mice
Objective—The A2B adenosine receptor is highly expressed in macrophages and vascular smooth muscle cells and has been established as an important regulator of inflammation and vascular adhesion. Recently, it has been demonstrated that A2BR deficiency enhances neointimal lesion formation after vascular injury. Therefore, we hypothesize that A2BR agonism protects against injury-induced intimal hyperplasia.
Methods and Results—Apolipoprotein E–deficient mice were fed a Western-type diet for 1 week, after which the left common carotid artery was denuded. Mice were treated with the A2B receptor agonist BAY60-6583 or vehicle control for 18 days. Interestingly, lumen stenosis as defined by the neointima/lumen ratio was inhibited by treatment with the A2B receptor agonist, caused by reduced smooth muscle cell proliferation. Collagen content was significantly increased in the BAY60-6583–treated mice, whereas macrophage content remained unchanged. In vitro, vascular smooth muscle cell proliferation decreased dose dependently whereas collagen content of cultured smooth muscle cells was increased by BAY60-6583.
Conclusion—Our data show that activation of the adenosine A2B receptor protects against vascular injury, while it also enhances plaque stability as indicated by increased collagen content. These outcomes thus point to A2B receptor agonism as a new therapeutic approach in the prevention of restenosis.
- Received October 17, 2011.
- Accepted June 14, 2012.
- © 2012 American Heart Association, Inc.