Loyer Xavier, Mallat Ziad, Boulanger Chantal M, Tedgui Alain
Université Paris Descartes, Sorbonne Paris Cité, Paris Cardiovascular Research Center - PARCC, INSERM UMR-S 970 , 56 rue Leblanc, 75015 Paris , France +33 1 53 98 80 06 ; +33 1 53 98 79 52 ;
Expert Opin Ther Targets. 2015 Apr;19(4):489-96. doi: 10.1517/14728222.2014.989835. Epub 2014 Dec 3.
Atherosclerosis is a chronic inflammatory disease of the arterial wall. A number of phenotypic cell changes occur during the development and progression of atherosclerosis. MicroRNAs (miRNAs) are key regulators of gene expression that act at the post-transcriptional level. They have been implicated in cardiovascular diseases, including atherosclerosis.
This review provides an overview of our knowledge about the expression and the roles of miRNAs in different cell types involved in atherosclerosis, with a focus on experimental strategies to modulate miRNA expression and their therapeutic effects in animal models of atherosclerosis. miRNA expression is regulated by inflammatory conditions and by shear stress in endothelial cells. Therapeutic approaches using antagomiR and miRNA mimic delivery and have been shown potentially effective in atherosclerosis. Moreover, a large body of evidence exists supporting a role for not only intracellular miRNA, but also miRNA carried by extracellular vesicles that are involved in inter-cellular communication through the transfer of miRNA.
Modulation of miRNA expression could represent novel innovative therapeutic approaches to treat atherosclerosis by targeting a single cell type or specific pathways. Future challenges will consist in deciphering the mechanisms involved in miRNA regulation and in improving cell-specific delivery of 'miR-drugs' by alternative strategies, including miRNA-enriched micro vesicles.
动脉粥样硬化是一种动脉壁的慢性炎症性疾病。在动脉粥样硬化的发生和发展过程中会出现一些细胞表型变化。微小RNA(miRNA)是在转录后水平发挥作用的基因表达关键调节因子。它们与包括动脉粥样硬化在内的心血管疾病有关。
本综述概述了我们对miRNA在参与动脉粥样硬化的不同细胞类型中的表达及作用的认识,重点关注调节miRNA表达的实验策略及其在动脉粥样硬化动物模型中的治疗效果。miRNA表达受内皮细胞中的炎症条件和剪切应力调节。使用抗miR和miRNA模拟物递送的治疗方法已显示在动脉粥样硬化中具有潜在疗效。此外,大量证据表明,不仅细胞内miRNA,而且细胞外囊泡携带的miRNA也通过miRNA转移参与细胞间通讯。
调节miRNA表达可能代表通过靶向单一细胞类型或特定途径治疗动脉粥样硬化的新型创新治疗方法。未来的挑战将在于解读miRNA调节所涉及的机制,以及通过替代策略(包括富含miRNA的微囊泡)改善“miR药物”的细胞特异性递送。