Novák Jan, Olejníčková Veronika, Tkáčová Nikola, Santulli Gaetano
2nd Department of Internal Medicine, St. Anne's University Hospital and Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5-building A18, Brno, 62500, Czech Republic.
Adv Exp Med Biol. 2015;887:79-100. doi: 10.1007/978-3-319-22380-3_5.
MicroRNAs (miRNAs, miRs) represent a group of powerful and versatile posttranscriptional regulators of gene expression being involved in the fine control of a plethora of physiological and pathological processes. Besides their well-established crucial roles in the regulation of cell cycle, embryogenesis or tumorigenesis, these tiny molecules have also been shown to participate in the regulation of lipid metabolism. In particular, miRs orchestrate cholesterol and fatty acids synthesis, transport, and degradation and low-density and high-density lipoprotein (LDL and HDL) formation. It is thus not surprising that they have also been reported to affect the development and progression of several lipid metabolism-related disorders including liver steatosis and atherosclerosis. Mounting evidence suggests that miRs might represent important "posttranscriptional hubs" of lipid metabolism, which means that one miR usually targets 3'-untranslated regions of various mRNAs that are involved in different steps of one precise metabolic/signaling pathway, e.g., one miR targets mRNAs of enzymes important for cholesterol synthesis, degradation, and transport. Therefore, changes in the levels of one key miR affect various steps of one pathway, which is thereby promoted or inhibited. This makes miRs potent future diagnostic and even therapeutic tools for personalized medicine. Within this chapter, the most prominent microRNAs involved in lipid metabolism, e.g., miR-27a/b, miR-33/33*, miR-122, miR-144, or miR-223, and their intracellular and extracellular functions will be extensively discussed, in particular focusing on their mechanistic role in the pathophysiology of atherosclerosis. Special emphasis will be given on miR-122, the first microRNA currently in clinical trials for the treatment of hepatitis C and on miR-223, the most abundant miR in lipoprotein particles.
微小RNA（miRNA，miR）是一类强大且多功能的基因表达转录后调节因子，参与众多生理和病理过程的精细调控。除了在细胞周期调控、胚胎发育或肿瘤发生中已确立的关键作用外，这些小分子还被证明参与脂质代谢的调节。特别是，miR协调胆固醇和脂肪酸的合成、运输和降解以及低密度和高密度脂蛋白（LDL和HDL）的形成。因此，据报道它们也会影响包括肝脂肪变性和动脉粥样硬化在内的几种脂质代谢相关疾病的发展和进程也就不足为奇了。越来越多的证据表明，miR可能代表脂质代谢的重要“转录后枢纽”，这意味着一个miR通常靶向参与一个精确代谢/信号通路不同步骤的各种mRNA的3'非翻译区，例如，一个miR靶向对胆固醇合成、降解和运输重要的酶的mRNA。因此，一种关键miR水平的变化会影响一条通路的各个步骤，从而促进或抑制该通路。这使得miR成为未来个性化医学中强有力的诊断甚至治疗工具。在本章中，将广泛讨论参与脂质代谢的最突出的微小RNA，例如miR-27a/b、miR-33/33*、miR-122、miR-144或miR-223，以及它们在细胞内和细胞外的功能，尤其关注它们在动脉粥样硬化病理生理学中的机制作用。将特别强调miR-122，它是目前首个进入丙型肝炎治疗临床试验的微小RNA，以及miR-223，它是脂蛋白颗粒中含量最丰富的miR。
