NOX1 Negatively Modulates Fibulin-5 in Vascular Smooth Muscle Cells to Affect Aortic Dissection
NOX1 Negatively Modulates Fibulin-5 in Vascular Smooth Muscle Cells to Affect Aortic Dissection
复制标题
NOX1 负向调节血管平滑肌细胞中的 Fibulin-5 影响主动脉夹层
DOI：
10.1248/bpb.b18-01012
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发表时间：
2019-09-01
影响因子：
2
通讯作者：
Hu, Zhipeng
中科院分区：
文献类型：
--
作者：
Hu, Xiaoping;Jiang, Wanli;Hu, Zhipeng
主动脉夹层（AD）疾病的特征是主动脉中膜变性。氧化应激在 AD 的发展中起着至关重要的作用。还原型烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶1（NOX1）缺乏可降低血管紧张素11诱导的主动脉夹层的发生率，但其机制仍有待进一步阐明。 AD患者中Fibulin-5表达降低，但其上游机制尚不清楚。本研究旨在阐明AD中NOX1和Fibulin-5之间的关系。结果显示，AD中NOX1和Fibulin-5的表达分别升高和降低。接下来，通过在体外采用功能获得和丧失的方法，NOX1 负向调节血管平滑肌细胞中的 Fibulin-5。此外，VAS2870 减弱的 NOX1 活性可以上调 Fibulin-5 的表达。这些发现表明 NOX1 是 AD 中 Fibulin-5 的负调节剂。
Aortic dissection (AD) diseases are characterized by degeneration of the aortic media. Oxidative stress plays a crucial role in the development of AD. Reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (NOX1) deficiency reduces the incidence of aortic dissection induced by angiotensin 11, but its mechanism remains to be further elucidated. The expression of Fibulin-5 is decreased in patients with AD, but its upstream mechanism is still unclear. This study was to clarify the relationship between NOX1 and Fibulin-5 in the AD. Results showed that the expressions of NOX1 and Fibulin-5 were increased and decreased in the AD, respectively. Next, by employing gain- and loss-of-function approaches in vitro, NOX1 negatively regulated Fibulin-5 in the vascular smooth muscle cells. Moreover, the blunted activity of NOX1 with VAS2870 could upregulate the expression of Fibulin-5. These findings indicate NOX1 is a negative modulator of Fibulin-5 in the AD.