CircTMEM165 facilitates endothelial repair by modulating mitochondrial fission via miR-192/SCP2 in vitro and in vivo
Yan Liu,
Yanyan Yang,
Min Li,
Xiuxiu Fu,
Xiangqin He,
Xiaoxin Li,
Jae Youl Cho,
Pei-feng Li,
Tao Yu
Affiliations
Yan Liu
Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, No. 38 Dengzhou Road, Qingdao 266021, People’s Republic of China; Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea
Yanyan Yang
Department of Immunology, School of Basic Medicine, Qingdao University, No. 308 Ningxia Road, Qingdao 266071, China
Min Li
Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, No. 38 Dengzhou Road, Qingdao 266021, People’s Republic of China
Xiuxiu Fu
Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, Qingdao 266000, China
Xiangqin He
Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, Qingdao 266000, China
Xiaoxin Li
Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, No. 38 Dengzhou Road, Qingdao 266021, People’s Republic of China
Jae Youl Cho
Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea
Pei-feng Li
Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, No. 38 Dengzhou Road, Qingdao 266021, People’s Republic of China
Tao Yu
Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, No. 38 Dengzhou Road, Qingdao 266021, People’s Republic of China; Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, Qingdao 266000, China; Corresponding author
Summary: Constitutive explorations indicate a correlation between circular RNAs (circRNAs) and cardiovascular diseases. However, the involvement of circRNAs in endothelial recuperation and in-stent restenosis (ISR) remains underexplored. CircTMEM165 has first been reported to be highly expressed in hypoxic human umbilical vein endothelial cells (HUVECs). Here, we identified that circTMEM165 was downregulated in ISR patients, inversely correlating with ISR severity. Functionally, circTMEM165 was found to be abundant in endothelial cells, inhibiting inflammation, and adhesion. Particularly, we first observed that circTMEM165 could alleviate HUVECs apoptosis and mitochondrial fission induced by lipopolysaccharide (LPS). Mechanistically, circTMEM165, as a miR-192-3p sponge, enhancing SCP2 expression, which serves as a critical regulator of HUVECs biological functions. Moreover, in vivo, circTMEM165 attenuated intimal hyperplasia and facilitated repair following classic rat carotid artery balloon injury model. These findings investigated the circTMEM165-miR-192-3p-SCP2 axis as a critical determinant of endothelial health and a potential biomarker and therapeutic target for vascular disorders.
