Overexpression of the P2Y 2 Purinoceptor in Intimal Lesions of the Rat Aorta

Abstract

Extracellular nucleotides, particularly ATP, are involved in the modulation of arterial vasomotricity via P2 purinoceptors present on smooth muscle and endothelial cells. These nucleotides could also be implicated in the smooth muscle cell hyperplasia observed in intimal lesions. In this study, we tried to define the potential role of the P2Y ₂ (P _2u ) purinoceptor by studying its expression in normal and balloon-injured rat aortas. The cloning of a rat P2Y ₂ cDNA from a rat smooth muscle cell cDNA library made it possible to study P2Y ₂ expression both by Northern blot and in situ hybridization. Northern blot experiments indicated that P2Y ₂ mRNA was present in rat medial aortic smooth muscle and in cultured rat aortic smooth muscle cells. In situ hybridization indicated that P2Y ₂ mRNA was present in endothelial cells of the intima and in some smooth muscle cells scattered throughout the media of adult rat aortas, while almost all medial smooth muscle cells of rat embryo aorta expressed this receptor. In contrast with adult aortic media, the majority of neointimal smooth muscle cells found in aortic intimal lesions either 8 or 20 days after balloon injury were positive for P2Y ₂ mRNA. Moreover, a subpopulation of neointimal cells localized at the luminal surface could be identified by a higher P2Y ₂ expression than the underlying neointimal smooth muscle cells. These data showing a strong expression of the P2Y ₂ purinoceptor in the neointima of injured arteries suggest that extracellular nucleotides may be involved, via this receptor, in the intimal hyperplasia and/or chronic constriction observed at the lesion site, and consequently in the restenotic process.