Tang Yuyan, Li Huaping, Chen Chen
Division of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Wuhan, China.
Front Cardiovasc Med. 2022 Apr 25;9:889743. doi: 10.3389/fcvm.2022.889743. eCollection 2022.
Atherosclerosis has been the main cause of disability and mortality in the world, resulting in a heavy medical burden for all countries. It is widely known to be a kind of chronic inflammatory disease in the blood walls, of which the key pathogenesis is the accumulation of immunologic cells in the lesion, foam cells formation, and eventually plaque rupture causing ischemia of various organs. Non-coding RNAs (ncRNAs) play a vital role in regulating the physiologic and pathophysiologic processes in cells. More and more studies have revealed that ncRNAs also participated in the development of atherosclerosis and regulated cellular phenotypes such as endothelial dysfunction, leukocyte recruitment, foam cells formation, and vascular smooth muscle cells phenotype-switching and apoptosis. Given the broad functions of ncRNAs in atherogenesis, they have become potential therapeutic targets. Apart from that, ncRNAs have become powerful blueprints to design new drugs. For example, RNA interference drugs were inspired by small interfering RNAs that exist in normal cellular physiologic processes and behave as negative regulators of specific proteins. For instance, inclisiran is a kind of RNAi drug targeting PCKS9 mRNA, which can lower the level of LDL-C and treat atherosclerosis. We introduce some recent research progresses on ncRNAs related to atherosclerotic pathophysiologic process and the current clinical trials of RNA drugs pointed at atherosclerosis.
动脉粥样硬化一直是全球致残和致死的主要原因,给各国带来了沉重的医疗负担。众所周知,它是一种血管壁慢性炎症性疾病,其关键发病机制是病变部位免疫细胞的积聚、泡沫细胞形成,最终导致斑块破裂,引发各器官缺血。非编码RNA(ncRNAs)在调节细胞的生理和病理生理过程中起着至关重要的作用。越来越多的研究表明,ncRNAs也参与了动脉粥样硬化的发展,并调节细胞表型,如内皮功能障碍、白细胞募集、泡沫细胞形成以及血管平滑肌细胞表型转换和凋亡。鉴于ncRNAs在动脉粥样硬化发生过程中的广泛功能,它们已成为潜在的治疗靶点。除此之外,ncRNAs已成为设计新药的有力蓝本。例如,RNA干扰药物的灵感来源于正常细胞生理过程中存在的小干扰RNA,它们作为特定蛋白质的负调节因子发挥作用。例如,英克西兰是一种靶向PCKS9 mRNA的RNAi药物,可降低低密度脂蛋白胆固醇(LDL-C)水平并治疗动脉粥样硬化。我们介绍了一些与动脉粥样硬化病理生理过程相关的ncRNAs的最新研究进展以及目前针对动脉粥样硬化的RNA药物临床试验情况。