IQGAP1 participates in endothelial cell apoptosis and regulates atherosclerosis by targeting YAP

Endothelial cell (EC) Apoptosis plays a crucial role in the onset and progression of atherosclerosis (AS). IQGAP1 is highly expressed in various tissues and affects cell growth, development and death. However, the complete elucidation of the influence of IQGAP1 on EC Apoptosis and AS remains unclear. This study endeavored to establish that IQGAP1 expression is augmented in the aortic wall of AS mice. Additionally, the present study demonstrated increased Bax and cleaved Caspase-3 expression along with notably reduced Bcl-2 expression within the aortic wall of mice with AS. After transfecting small interfering RNA of IQGAP1 (Si-IQGAP1) into normal or palmitic acid (PA)-treated human umbilical vein endothelial cells (HUVECs) cultured in vitro, the apoptotic rate decreased. Furthermore, western blot analysis demonstrated reduced expression pro-apoptotic proteins, namely Bax and cleaved Caspase-3, accompanied by increased expression of the anti-apoptotic protein Bcl-2. Simultaneously, the key protein of the Hippo signaling pathway, YAP, showed increased expression, whereas phosphorylated YAP expression decreased. However, subsequent to the overexpression of IQGAP1, the trajectory of the aforementioned parameters was reversed. In addition, the knockdown of YAP promoted the Apoptosis rate in co-transfected Si-IQGAP1 and Si-YAP group. In conclusion, IQGAP1 potentially facilitates Apoptosis in HUVECs, thereby contributing to AS initiation and progression. This mechanism may be partly attributed to the modulation of pivotal proteins, including YAP.