Direct evidence for the importance of endothelium-derived nitric oxide in vascular remodeling
Direct evidence for the importance of endothelium-derived nitric oxide in vascular remodeling
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DOI：
10.1172/jci1699
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发表时间：
1998-02-15
影响因子：
15.9
通讯作者：
Sessa, WC
中科院分区：
文献类型：
--
作者：
Rudic, RD;Shesely, EG;Sessa, WC
血管内皮介导血管响应血流动力学变化而改变其结构的能力;然而，对负责血管重塑的特定内皮源性因子知之甚少。在此，我们表明内皮源性一氧化氮（NO）是控制血管重塑的主要内皮源性介质。在对颈外动脉结扎的反应中，靶向破坏内皮型一氧化氮合酶基因（eNOS）的小鼠确实使其同侧颈总动脉重塑，而野生型小鼠则是如此。相反，eNOS突变小鼠显示出血管壁厚度的反常增加，伴随着动脉壁的增生反应。这些研究结果表明，内源性NO作为血管平滑肌增殖的负调节因子在响应重塑刺激中起着关键作用。此外，我们的数据表明，NOS/NO通路中的原发性缺陷可以促进异常重塑，并可能促进与高血压和动脉粥样硬化等复杂疾病相关的血管壁形态的病理变化。
The vascular endothelium mediates the ability of blood vessels to alter their architecture in response to hemodynamic changes; however, the specific endothelial-derived factors that are responsible for vascular remodeling are poorly understood, Here we show that endothelial-derived nitric oxide (NO) is a major endothelial-derived mediator controlling vascular remodeling, In response to external carotid artery ligation, mice with targeted disruption of the endothelial nitric oxide synthase gene (eNOS) did Rot remodel their ipsilateral common carotid arteries whereas wild-type mice did, Rather, the eNOS mutant mice displayed a paradoxical increase in wall thickness accompanied by a hyperplastic response of the arterial wall. These findings demonstrate a critical role for endogenous NO as a negative regulator of vascular smooth muscle proliferation in response to a remodeling stimulus, Furthermore, our data suggests that a primary defect in the NOS/NO pathway can promote abnormal remodeling and may facilitate pathological changes in vessel wall morphology associated with complex diseases such as hypertension and atherosclerosis.