Tong Kind-Leng, Tan Ke-En, Lim Yat-Yuen, Tien Xin-Yi, Wong Pooi-Fong
Department of Pharmacology, Faculty of Medicine, Universiti Malaya, 50603, Kuala Lumpur, Malaysia.
Institute of Biological Sciences, Faculty of Science, Universiti Malaya, 50603, Kuala Lumpur, Malaysia.
Mol Cell Biochem. 2022 Dec;477(12):2703-2733. doi: 10.1007/s11010-022-04455-8. Epub 2022 May 23.
Atherosclerosis is the major cause of coronary artery disease (CAD) which includes unstable angina, myocardial infarction, and heart failure. The onset of atherogenesis, a process of atherosclerotic lesion formation in the intima of arteries, is driven by lipid accumulation, a vicious cycle of reactive oxygen species (ROS)-induced oxidative stress and inflammatory reactions leading to endothelial cell (EC) dysfunction, vascular smooth muscle cell (VSMC) activation, and foam cell formation which further fuel plaque formation and destabilization. In recent years, there is a surge in the number of publications reporting the involvement of circular RNAs (circRNAs) in the pathogenesis of cardiovascular diseases, cancers, and metabolic syndromes. These studies have advanced our understanding on the biological functions of circRNAs. One of the most common mechanism of action of circRNAs reported is the sponging of microRNAs (miRNAs) by binding to the miRNAs response element (MRE), thereby indirectly increases the transcription of their target messenger RNAs (mRNAs). Individual networks of circRNA-miRNA-mRNA associated with atherogenesis have been extensively reported, however, there is a need to connect these findings for a complete overview. This review aims to provide an update on atherogenesis-related circRNAs and analyze the circRNA-miRNA-mRNA interactions in atherogenesis. The atherogenic mechanisms and clinical relevance of each atherogenesis-related circRNA were systematically discussed for better understanding of the knowledge gap in this area.
动脉粥样硬化是冠状动脉疾病(CAD)的主要病因,冠状动脉疾病包括不稳定型心绞痛、心肌梗死和心力衰竭。动脉粥样硬化的发生,即动脉内膜中动脉粥样硬化病变形成的过程,是由脂质积累驱动的,这是一个由活性氧(ROS)诱导的氧化应激和炎症反应的恶性循环,导致内皮细胞(EC)功能障碍、血管平滑肌细胞(VSMC)活化和泡沫细胞形成,进而进一步促进斑块形成和不稳定。近年来,报道环状RNA(circRNAs)参与心血管疾病、癌症和代谢综合征发病机制的出版物数量激增。这些研究增进了我们对circRNAs生物学功能的理解。报道的circRNAs最常见的作用机制之一是通过与微小RNA(miRNAs)反应元件(MRE)结合来“海绵化”miRNAs,从而间接增加其靶信使RNA(mRNAs)的转录。与动脉粥样硬化相关的circRNA-miRNA-mRNA个体网络已被广泛报道,然而,需要将这些发现联系起来以获得完整的概述。本综述旨在提供动脉粥样硬化相关circRNAs的最新信息,并分析动脉粥样硬化中circRNA-miRNA-mRNA的相互作用。系统地讨论了每种动脉粥样硬化相关circRNA的致动脉粥样硬化机制和临床相关性,以便更好地了解该领域的知识空白。