MicroRNA-122 promotes endothelial cell apoptosis by targeting XIAP: Therapeutic implication for atherosclerosis

In this study, we found that miR-122 expression was increased in the aortic ECs of ApoE−/− mice fed with a high-fat diet (HFD), as compared to normal-diet (ND), implying a potential association between miR-122 elevation and atherogenesis. In addition, in vitro, miR-122 expression was also induced in human aortic ECs (HAECs) by the treatment of oxidized low-density lipoprotein (ox-LDL), a common atherogenic factor. Functionally, miR-122 knockdown suppressed ox-LDL-induced apoptosis of HAECs, suggesting a pro-apoptotic role of miR-122 in HAECs under this pro-atherogenic condition. Further evidence revealed that the X-linked inhibitor-of-apoptosis protein (XIAP) was directly targeted and suppressed by miR-122 in HAECs, and more importantly, XIAP knockdown diminished miR-122 effect on apoptosis, thus establishing XIAP as a prominent target that mediates miR-122 regulation of the apoptosis of HAECs. Together, these results may identify miR-122 as a novel regulator in EC apoptosis, which offers it as a possible target for therapeutic interventions of atherosclerosis.

Source: Life Sciences - June 19, 2019 Category: Biology Source Type: research