TIPE1 accelerates atherogenesis by inducing endothelial dysfunction in response to oxidative stress

Atherosclerosis is an inflammatory disease of the arterial wall, which involves endothelial cells and immune cells. Endothelial dysfunction has been considered an important step in the initiation of the disease. TIPE1 is a newly identified protein of the TIPE family, and plays a vital role in inflammation and tumorigenesis. However, its role in atherogenesis remains unclear. In this study, we demonstrated that TIPE1 promoted atherogenesis by inducing endothelial dysfunction. When human umbilical vein endothelial cells (HUVECs) were exposed to oxidative stress, the level of TIPE1 was significantly up-regulated, and the ROS generation markedly increased in TIPE1 over-expressing HUVECs. As a result, the growth of HUVECs was inhibited, and the apoptosis was enhanced. However, the cell contact ability between HUVECs and THP-1 cells were augmented due to the up-regulation of adhesion molecules such as E -selectin and ICAM-1 induced by TIPE1 overexpression. Importantly, ApoE − / − mice injected with TIPE1 recombinant lentivirus developed significantly severe atherosclerosis accompanied by hyperglycemia, hypercholesterolemia and increased white blood count. These findings indicated that excessive ROS induced by the overexpression of TIPE1 in endothelial cells accelerated the process of atherogenesis. • TIPE1 expression is significantly enhanced in HUVECs exposed to oxidative stress. • The increased TIPE1 expression in HUVECs results in endothelial dysfunction. • As a result, the ApoE -/- mice injected with recombinant lentivirus-TIPE1 are liable to develop atherosclerotic plaques. • Our findings indicate that excessive ROS induced by the overexpression of TIPE1 in HUVECs accelerates atherogenesis.