CircTMEM165 Facilitates Vascular Endothelial Repair by Modulating Mitochondrial Fission via miR-192/SCP2 in vitro and in vivo

Abstract

Constitutive explorations have demonstrated that circular RNAs (circRNAs) are closely related to cardiovascular diseases. However, few studies have identified regulatory roles of circRNAs in endothelial repair. In particular, circTMEM165 has first been reported to be highly expressed in hypoxic human umbilical vein endothelial cells (HUVECs), indicating it to be closely linked with endothelial functions and atherosclerosis. Here, we explored the main biological functions of circTMEM165 and its regulatory mechanism in atherosclerosis. We identified that circTMEM165 was downregulated in patients with atherosclerosis and negatively associated with atherosclerosis progression. Functionally, circTMEM165 was found to be abundant in endothelial cells, inhibiting inflammation and adhesion in HUVECs. Particularly, we first observed that lipopolysaccharide (LPS) could induce HUVEC apoptosis and mitochondrial fission, and circTMEM165 was later found to alleviate these effects. Mechanistically, circTMEM165, as a miR-192-3p sponge, upregulated the downstream expression of SCP2, which serves as critical regulator of biological functions of HUVECs. Moreover, the classic rat carotid artery balloon injury model demonstrated that circTMEM165 reduced apoptosis and intimal hyperplasia in vivo. These findings demonstrated the specific role of the circTMEM165/miR-192-3p/SCP2 pathway in regulating endothelial function and indicated that these molecules served as promising targets for the prediction and diagnosis of vascular diseases. Funding Information: This work was supported by The National Natural Science Foundation of China (grant no. 81870331), and The Qingdao municipal science and technology bureau project (grant no. 21-1-4-rkjk-12-nsh). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: This study was approved by the Ethical Committee of Qingdao University and conducted in accordance with the Declaration of Helsinki. All human subjects provided signed informed consent. And the animal experiments approved by Qingdao University Laboratory Animal Welfare Ethics Committee (No. 201809SD18202012014).