Yes-associated protein 1 up-regulation inhibits apoptosis of aortic dissection vascular smooth muscle cells

Abstract

Objective To investigate the role of Yes-associated protein 1 (YAP1) expression in apoptosis of vascular smooth muscle cells (VSMCs) and pathogenesis of aortic dissection (AD). Methods AD rat model was established to compare apoptosis and the expression of YAP1 within vascular tissues against normal controlled rats.In vitro cultured rat thoracic VSMCs were divided into control, cyclic stretch, cyclic stretch + pIRES2-blank and cyclic stretch + pIRES2-YAP1 groups. Cell apoptosis rate, YAP1 and Survivin expression were measured. AD rats were divided into model, Ad-NC injection, and Ad-YAP1 injection groups for comparing VSMCs apoptosis, AD formation rate, diameter and length. Results The AD rats of AD modle groupe is 43.1% [AD diameter is (6.21±1.13) mm, AD length is (9.25±1.77) mm]; The AD rats of Ad-NC-injecting groupe is 43.1% [AD diameter is (6.21±1.13) mm, AD length is (9.25±1.77) mm]; The AD rats of Ad-YAP1-injecting groupe is 43.1% [AD diameter is (6.21±1.13) mm, AD length is (9.25±1.77) mm]. Compared to control group, AD rats had elevated vascular cell apoptosis, and down-regulated YAP1 expression. Cyclic stretch significantly induced VSMCs apoptosis. YAP1 over-expression up-regulated Survivin and antagonized cyclic stretch-induced cell apoptosis. Injection of Ad-YAP1 via the tail vein significantly up-regulated YAP1 and Survivin expression, and decreased apoptosis, AD formation rate and AD diameter/length in vascular tissues of rat AD models. Conclusion YAP1 down-regulation plays a role in facilitating VSMCs apoptosis and AD pathogenesis. Up-regulation of YAP1 decreases VSMCs apoptosis and AD formation. Key words: Yes-associated protein 1; Hippo-Yes-associated protein; Vascular smooth muscle cells; Aortic dissection; Apoptosis