Vasoactive substances regulate vascular smooth muscle cell apoptosis - Countervailing influences of nitric oxide and angiotensin II
Vasoactive substances regulate vascular smooth muscle cell apoptosis - Countervailing influences of nitric oxide and angiotensin II
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DOI：
10.1161/01.res.79.4.748
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发表时间：
1996-10-01
影响因子：
20.1
通讯作者：
Gibbons, GH
中科院分区：
文献类型：
--
作者：
Pollman, MJ;Yamada, T;Gibbons, GH
本研究验证了血管平滑肌细胞（VSMC）凋亡的控制是由血管活性物质如NO和血管紧张素II（Aug II）之间的拮抗平衡调节的假设。此外，据推测，参与调节血管张力的细胞信号传导途径也与程序性细胞死亡的调节偶联。使用体外模型系统，我们证明，除了NO供体分子S-亚硝基-N-乙酰青霉胺或硝普钠的VSMC剂量依赖性诱导细胞凋亡的DNA梯状记录和定量的细胞染色质形态分析。鸟苷酸环化酶信号通路在NO诱导的细胞凋亡中的介导作用通过（1）8-溴-cGMP类似物诱导的细胞凋亡，（2）cGMP特异性磷酸二酯酶抑制剂增强NO诱导的细胞凋亡来证明。和（3）通过抑制cGMP依赖性蛋白激酶I α来防止NO诱导的细胞凋亡。与此相反，血管紧张素II直接拮抗NO供体和cGMP类似物诱导的细胞凋亡，通过激活的I型血管紧张素II受体。这些研究结果表明，NO和血管紧张素II之间的抵消平衡，可能会决定血管壁内的整体细胞群体，通过调节基因程序，决定细胞死亡以及细胞生长。
This study tests the hypothesis that the control of vascular smooth muscle cell (VSMC) apoptosis is regulated by the antagonistic balance between vasoactive substances such as NO and angiotensin II (Aug II). Moreover, it is postulated that the cellular signaling pathways involved in regulating vessel tone are also coupled to the regulation of programmed cell death. Using an in vitro model system, we documented that the addition of NO donor molecules S-nitroso-N-acetylpenicillamine or sodium nitroprusside to VSMC dose-dependently induced apoptosis as documented by DNA laddering and quantified by analysis of cellular chromatin morphology. The mediator role of the guanylate cyclase signaling pathway in NO-induced apoptosis was evidenced by (1) induction of apoptosis by the 8-bromo-cGMP analogue, (2) potentiation of NO-induced apoptosis by cGMP-specific phosphodiesterase inhibition. and (3) the prevention of NO-induced apoptosis by the inhibition of the cGMP-dependent protein kinase I alpha. In contrast, Ang II directly antagonized NO donor- and cGMP analogue-induced apoptosis via activation of the type I Ang II receptor. These findings suggest that the countervailing balance between NO and Ang II may determine the overall cell population within the vessel wall by regulating genetic programs determining cell death as well as cell growth.