OVEREXPRESSION OF THE P2Y(2) PURINOCEPTOR IN INTIMAL LESIONS OF THE RAT AORTA

Extracellular nucleotides, particularly ATP, are involved in the modul ation of arterial vasomotricity via P2 purinoceptors present on smooth muscle and endothelial cells. These nucleotides could also be implica ted 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-inj ured rat aortas. The cloning of a rat P2Y(2) CDNA from a rat smooth mu scle cell cDNA library made it possible to study P2Y(2) expression bot h by Northern blot and in situ hybridization. Northern blot experiment s indicated that P2Y(2) mRNA was present in rat medial aortic smooth m uscle and in cultured rat aortic smooth muscle cells. In situ hybridiz ation indicated that P2Y(2) mRNA was present in endothelial cells of t he intima and in some smooth muscle cells scattered throughout the med ia of adult rat aortas, while almost all medial smooth muscle cells of rat embryo aorta expressed this receptor. In contrast with adult aort ic media, the majority of neointimal smooch muscle cells found in aort ic intimal lesions either 8 or 20 days after balloon injury were posit ive for P2Y(2) mRNA. Moreover, a subpopulation of neointimal cells loc alized at the luminal surface could be identified by a higher P2Y(2) e xpression than the underlying neointimal smooth muscle cells. These da ta showing a strong expression of the P2Y(2) purinoceptor in the neoin tima. of injured arteries su est that extracellular DP nucleotides may be involved, via this receptor, in the intimal hyperplasia and/or chr onic constriction observed at the lesion site. and consequently in the restenotic process.