Overexpression of angiotensin II type 1 receptor-associated protein promotes apoptosis of vascular smooth muscle cells and inhibits carotid intimal hyperplasia

Objective To investigate the effect and mechanism of angiotensin Ⅱ type 1 receptor-associated protein (ATRAP) on the apoptosis of vascular smooth muscle cell (VSMC) and the inhibition of carotid intimal hyperplasia. Methods Adenovirus of overexpression of ATRAP was constructed and transfected into cultured VSMC and balloon injured carotid common arteries. TUNEL, real-time PCR and western blot were used to detect cell apoptosis and the expression of apoptosis-related genes, respectively. Results The apoptotic rate of VSMC was significantly increased in the ATRAP transfection group (Adv.ATRAP) compared with the control group (Adv.GFP) [(11.50±1.66)% vs (1.13±0.27)% in Ang Ⅱ treatment groups, P<0.05;(13.17±0.48)% vs (1.20±0.17)% in non-Ang Ⅱ treatment groups, P<0.05], and the presence or absence of angiotensin(Ang Ⅱ) did not affect the extent of apoptosis. Overexpression of ATRAP inhibited the phosphorylation of Akt activated by stimulation. The increased apoptosis of VSMC in Adv.ATRAP group was significantly attenuated by PTEN inhibitor (bpV) which enhanced the phosphorylation of Akt [(11.50±1.66)% vs (1.81±0.19)% in Ang Ⅱ treatment groups, P<0.05;(13.17±0.48)% vs (1.45±0.15)% in non-Ang Ⅱ treatment groups, P<0.05]. Neointimal formation was inhibited after incubation with Adv.ATRAP in balloon injured arteries after 14 days compared with Adv.GFP group (P<0.05). Conclusion The overexpression of ATRAP might promote the apoptosis of VSMC, thereby inhibit intimal hyperplasia after carotid balloon injury. Key words: Angiotensin Ⅱ type 1 receptor-associated protein; Vascular smooth muscle cells; Apoptosis; Balloon injury