The potential role and mechanism of circRNAs in foam cell formation

Wujun Chen; Yihui Liu; Ling Li; Bing Liang; Shuai Wang; Xiaodan Xu; Dongming Xing; Xiaolin Wu

doi:10.1016/j.ncrna.2023.03.005

The potential role and mechanism of circRNAs in foam cell formation

Noncoding RNA Res. 2023 Mar 21;8(3):315-325. doi: 10.1016/j.ncrna.2023.03.005. eCollection 2023 Sep.

Authors

Wujun Chen¹, Yihui Liu², Ling Li³, Bing Liang¹, Shuai Wang², Xiaodan Xu⁴, Dongming Xing^{1

5}, Xiaolin Wu¹

Affiliations

¹ Department of Orthopedics, Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, Shandong, 266071, China.
² Department of Radiotherapy, Affiliated Hospital of Weifang Medical University, Key Laboratory of Precision Radiation Therapy for Tumors in Weifang City, School of Medical Imaging, Weifang Medical University, Weifang, Shandong, 261031, China.
³ Department of Pharmacy, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, 519000, China.
⁴ Department of Pathology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, China.
⁵ School of Life Sciences, Tsinghua University, Beijing, 100084, China.

Abstract

Atherosclerosis is a significant risk factor for coronary heart disease (CHD) and myocardial infarction (MI). Atherosclerosis develops during foam cell generation, which is caused by an imbalance in cholesterol uptake, esterification, and efflux. LOX-1, SR-A1, and CD36 all increased cholesterol uptake. ACAT1 and ACAT2 promote free cholesterol (FC) esterification to cholesteryl esters (CE). The hydrolysis of CE to FC was aided by nCEH. FC efflux was promoted by ABCA1, ABCG1, ADAM10, and apoA-I. SR-BI promotes not only cholesterol uptake but also FC efflux. Circular RNAs (circRNAs), which are single-stranded RNAs with a closed covalent circular structure, have emerged as promising biomarkers and therapeutic targets for atherosclerosis due to their highly tissue, cell, and disease state-specific expression profiles. Numerous studies have shown that circRNAs regulate foam cell formation, acting as miRNA sponges to influence atherosclerosis development by regulating the expression of SR-A1, CD36, ACAT2, ABCA1, ABCG1, ADAM10, apoA-I, SR-B1. Several circRNAs, including circ-Wdr91, circ 0004104, circRNA0044073, circRNA_0001805, circDENND1B, circRSF1, circ 0001445, and circRNA 102682, are potential biomarkers for atherosclerosis to better evaluate cardiovascular risk. It is difficult to deliver synthetic therapeutic circRNAs to the desired target tissues. Nanotechnology, such as GA-RM/GZ/PL, may be an important solution to this problem. In this review, we focus on the potential role and mechanism of circRNA/miRNA axis in foam cell formation in the hopes of discovering new targets for the diagnosis, prevention, and treatment of atherosclerosis.

Keywords: Atherosclerosis; Cholesterol efflux; Cholesterol esterification; Cholesterol uptake; CircRNA/miRNA axis.

Publication types

Review