Endothelium-derived Cdk5 deficit aggravates air pollution-induced peripheral vasoconstriction through AT1R upregulation.
Endothelium-derived Cdk5 deficit aggravates air pollution-induced peripheral vasoconstriction through AT1R upregulation.
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DOI：
10.1016/j.ecoenv.2021.112314
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发表时间：
2021-05
影响因子：
6.8
通讯作者：
Lu Lu-Lu;Lin Yang;Yaping Lu;Qin Jiang;Cuirong Wang;Cui-Qing Liu;Nan Xu;Shan Jiang;Gang Zhang-G
中科院分区：
文献类型：
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作者：
Lu Lu-Lu;Lin Yang;Yaping Lu;Qin Jiang;Cuirong Wang;Cui-Qing Liu;Nan Xu;Shan Jiang;Gang Zhang-G
PM2.5进入循环系统，增加全身血管功能障碍的风险。作为抵御外界刺激的第一线屏障，血管内皮细胞对PM2.5暴露的生物学反应的分子机制尚不清楚.在这项研究中，4周龄的小鼠暴露于杭州“真实的”空气中的PM2.5 2个月，发现显示支气管和肺泡损伤。重要的是，在本研究中，我们已经证明Cdk 5缺陷通过血管紧张素II 1型受体在血管紧张素II刺激下诱导Cdh 5-cre; Cdk 5 f/n小鼠外周血管收缩。在大脑中，Cdk 5缺陷增加了在外部压力下髓小动脉的生肌活性。另一方面，在暴露于PM2.5的Cdh 5-cre; Cdk 5 f/n小鼠中没有观察到脑血流量和行为模式的变化。因此，我们目前的研究结果表明，CDK 5在内皮细胞生长，迁移和分子转导中起着重要作用，也是血管内皮细胞对PM2.5反应的传感器。
PM2.5infiltrates into circulation and increases the risk of systemic vascular dysfunction. As the first-line barrier against external stimuli, the molecular mechanism of the biological response of vascular endothelial cells to PM2.5exposure remains unclear. In this study, 4-week-old mice were exposed to Hangzhou ‘real’ airborne PM2.5for 2 months and were found to display bronchial and alveolar damage. Importantly, in the present study, we have demonstrated thatCdk5deficit induced peripheral vasoconstriction through angiotensin II type 1 receptor under angiotensin II stimulation inCdh5-cre;Cdk5f/nmice. In the brain,Cdk5deficit increased the myogenic activity in the medullary arterioles under external pressure. On the other hand, no changes in cerebral blood flow and behavior patterns were observed in theCdh5-cre;Cdk5f/nmice exposed to PM2.5. Therefore, our current findings indicate that CDK5 plays an important role in endothelium cell growth, migration, and molecular transduction, which is also a sensor for the response of vascular endothelial cells to PM2.5.