Endothelium-derived Cdk5 deficit aggravates air pollution-induced peripheral vasoconstriction through AT1R upregulation.

PM 2.5 infiltrates 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 PM 2.5 exposure remains unclear. In this study, 4-week-old mice were exposed to Hangzhou 'real' airborne PM 2.5 for 2 months and were found to display bronchial and alveolar damage. Importantly, in the present study, we have demonstrated that Cdk5 deficit induced peripheral vasoconstriction through angiotensin II type 1 receptor under angiotensin II stimulation in Cdh5-cre;Cdk5 ^f/n mice. In the brain, Cdk5 deficit 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 the Cdh5-cre;Cdk5 ^f/n mice exposed to PM 2.5. 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 PM 2.5. • Cdk5 deficit aggravates PM 2.5 -induced lung injury in Cdh5-cre;Cdk5^f/n mice. • Deficit of Cdk5 aggravates peripheral vasoconstriction by PM 2.5 through AT1R-mediated signal in mice. • PM 2.5 exposure increases sensitivity of medullary arterioles to external pressure in Cdh5-cre;Cdk5^f/n mice. • PM 2.5 has no effect on vasodilation of thoracic aorta, cognitive and emotional behavior patterns upon Cdk5 deficit. [ABSTRACT FROM AUTHOR]