Seye C I, Gadeau A P, Daret D, Dupuch F, Alzieu P, Capron L, Desgranges C
Unité 441 d'Athérosclérose de l'Institut National de la Santé et de la Recherche Médicale, Pessac, France.
Arterioscler Thromb Vasc Biol. 1997 Dec;17(12):3602-10. doi: 10.1161/01.atv.17.12.3602.
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 P2Y2 (P2u) purinoceptor by studying its expression in normal and balloon-injured rat aortas. The cloning of a rat P2Y2 cDNA from a rat smooth muscle cell cDNA library made it possible to study P2Y2 expression both by Northern blot and in situ hybridization. Northern blot experiments indicated that P2Y2 mRNA was present in rat medial aortic smooth muscle and in cultured rat aortic smooth muscle cells. In situ hybridization indicated that P2Y2 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 P2Y2 mRNA. Moreover, a subpopulation of neointimal cells localized at the luminal surface could be identified by a higher P2Y2 expression than the underlying neointimal smooth muscle cells. These data showing a strong expression of the P2Y2 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.
细胞外核苷酸，尤其是三磷酸腺苷（ATP），通过平滑肌和内皮细胞上存在的P2嘌呤受体参与动脉血管舒缩功能的调节。这些核苷酸也可能与内膜病变中观察到的平滑肌细胞增生有关。在本研究中，我们试图通过研究P2Y2（P2u）嘌呤受体在正常和球囊损伤大鼠主动脉中的表达来确定其潜在作用。从大鼠平滑肌细胞cDNA文库中克隆大鼠P2Y2 cDNA，使得通过Northern印迹法和原位杂交法研究P2Y2表达成为可能。Northern印迹实验表明，P2Y2 mRNA存在于大鼠主动脉中层平滑肌和培养的大鼠主动脉平滑肌细胞中。原位杂交表明，P2Y2 mRNA存在于成年大鼠主动脉内膜的内皮细胞以及整个中膜中散在的一些平滑肌细胞中，而大鼠胚胎主动脉的几乎所有中膜平滑肌细胞都表达该受体。与成年主动脉中膜不同，在球囊损伤后8天或20天的主动脉内膜病变中发现的大多数新生内膜平滑肌细胞P2Y2 mRNA呈阳性。此外，位于管腔表面的新生内膜细胞亚群可通过比其下方新生内膜平滑肌细胞更高的P2Y2表达来鉴定。这些数据表明P2Y2嘌呤受体在损伤动脉的新生内膜中强烈表达，提示细胞外核苷酸可能通过该受体参与病变部位观察到的内膜增生和/或慢性收缩，进而参与再狭窄过程。
