期刊
KIDNEY INTERNATIONAL
卷 81, 期 3, 页码 256-265出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ki.2011.326
关键词
arteriosclerosis; cardiovascular; vascular calcification
资金
- Deutsche Forschungsgemeinschaft (DFG) [972/11-2]
- Sonnenfeld Stiftung
- Nationales Genomforschungsnetzwerk
- Syskid
Purinergic signaling has a crucial role in different vascular processes. The endothelial-derived vasoconstrictor uridine adenosine tetraphosphate (Up(4)A) is a potent activator of the purinoceptor P2Y and is released under pathological conditions. Here we sought to measure purinergic effects on vascular calcification and initially found that Up(4)A plasma concentrations are increased in patients with chronic kidney disease. Exploring this further we found that exogenous Up(4)A enhanced mineral deposition under calcifying conditions ex vivo in rat and mouse aortic rings and in vitro in rat vascular smooth muscle cells. The addition of Up(4)A increased the expression of different genes specific for osteochondrogenic vascular smooth muscle cells such as Cbfa1, while decreasing the expression of SM22 alpha, a marker specific for vascular smooth muscle cells. The influence of different P2Y antagonists on Up(4)A-mediated process indicated that P2Y(2/6) receptors may be involved. Mechanisms downstream of P2Y signaling involved phosphorylation of the mitogen-activated kinases MEK and ERK1/2. Thus, Up(4)A activation of P2Y influences phenotypic transdifferentiation of vascular smooth muscle cells to osteochondrogenic cells, suggesting that purinergic signaling may be involved in vascular calcification. Kidney International (2012) 81, 256-265; doi: 10.1038/ki.2011.326; published online 28 September 2011
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据