Adenosine A _2B receptor agonism inhibits neointimal lesion development after arterial injury in apolipoprotein E-deficient mice

Objective-The A _2B adenosine receptor (A _2BR) 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 A _2BR deficiency enhances neointimal lesion formation after vascular injury. Therefore, we hypothesize that A _2BR 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 A _2B 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 A _2B 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 A _2B receptor protects against vascular injury, while it also enhances plaque stability as indicated by increased collagen content. These outcomes thus point to A _2B receptor agonism as a new therapeutic approach in the prevention of restenosis.