Institute for Cardiovascular Prevention, Ludwig-Maximilians-University Munich and DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Pettenkoferstrasse 9, 80336 Munich, Germany.
Nat Rev Cardiol. 2015 Jun;12(6):361-74. doi: 10.1038/nrcardio.2015.38. Epub 2015 Apr 7.
Atherosclerosis is characterised by the accumulation of lipid-laden macrophages in atherosclerotic lesions and occurs preferentially at arterial branching points, which are prone to inflammation during hyperlipidaemic stress. The increased susceptibility at branching sites of arteries is attributable to poor adaptation of arterial endothelial cells to disturbed blood flow. In the past 5 years, several studies have provided mechanistic insights into the regulatory roles of microRNAs (miRNAs) in inflammatory activation, proliferation, and regeneration of endothelial cells during this maladaptive process. The intercellular transfer of vesicle-bound miRNAs contributes to arterial homeostasis, and the combinatorial effect of multiple miRNAs controls the unresolved inflammation orchestrated by macrophages in atherosclerotic lesions. In this Review, we highlight the miRNA-dependent regulation of the endothelial phenotype and the proliferative reserve that occurs in response to altered haemodynamic conditions as a prerequisite for atherogenic inflammation. In particular, we discuss the regulation of transcriptional modules by miRNAs and the protective role of complementary strand pairs, which encompasses remote miRNA signalling. In addition, we review the roles of miRNA tandems and describe the relevance of RNA target selection and competition to the behaviour of lesional macrophages. Elucidating miRNA-mediated regulatory mechanisms can aid the development of novel diagnostic and therapeutic strategies for atherosclerosis.
动脉粥样硬化的特征是富含脂质的巨噬细胞在动脉粥样硬化病变中的积累，并且优先发生在动脉分支点，这些分支点在高脂血症应激时容易发生炎症。动脉分支处的易感性增加归因于动脉内皮细胞对血流紊乱的适应性差。在过去的 5 年中，有几项研究提供了有关 microRNAs（miRNAs）在炎症激活、内皮细胞增殖和在这个失调过程中再生中的调节作用的机制见解。囊泡结合的 miRNAs 的细胞间转移有助于动脉稳态，并且多个 miRNAs 的组合效应控制着动脉粥样硬化病变中巨噬细胞协调的未解决的炎症。在这篇综述中，我们强调了 miRNA 依赖性调节内皮表型和增殖储备的作用，这是动脉粥样硬化炎症发生的先决条件。特别是，我们讨论了 miRNA 对转录模块的调节作用以及互补链对的保护作用，这包含了远程 miRNA 信号。此外，我们还回顾了 miRNA 串联的作用，并描述了 RNA 靶标选择和竞争对病变巨噬细胞行为的相关性。阐明 miRNA 介导的调节机制可以帮助开发动脉粥样硬化的新的诊断和治疗策略。
