Department of Pharmacology and Therapeutics, King's College London, London SE5 9NU, UK.
Cardiovascular Division, Faculty of Life Sciences and Medicine, King's College London, London SE5 9NU, UK.
J Mol Cell Cardiol. 2018 Sep;122:98-113. doi: 10.1016/j.yjmcc.2018.08.004. Epub 2018 Aug 8.
Atherosclerosis, a chronic inflammatory condition that is characterized by the accumulation of lipid-loaded macrophages, occurs preferentially at the arterial branching points where disturbed flow is prominent. The pathogenesis of atherosclerotic lesion formation is a multistage process involving multiple cell types, inflammatory mediators and hemodynamic forces in the vessel wall in response to atherogenic stimuli. Researches from the past decade have uncovered the critical roles of microRNAs (miRNAs) in regulating multiple pathophysiological effects and signaling pathways in endothelial cells (ECs), vascular smooth muscle cells (VSMCs), macrophages and lipid homeostasis, which are key in atherosclerotic lesion formation. The expression of these miRNAs are either in response to biomechanical (flow-responsive) or biochemical (non-flow-responsive) stimuli. Recent evidences also indicate an important role for long non-coding RNAs (lncRNAs) in mediating several atherosclerotic processes. In this review, we provide a detailed summary on the current paradigms in miRNA-dependent regulation, the emerging role of lncRNAs in the initiation and progression of atherosclerosis, and clinical interventions targeting these in an attempt to develop novel diagnostics and treatments for atherosclerosis.
动脉粥样硬化是一种慢性炎症性疾病，其特征是脂质负荷巨噬细胞的积累，优先发生在血流紊乱明显的动脉分支处。动脉粥样硬化病变形成的发病机制是一个多阶段的过程，涉及多种细胞类型、炎症介质和血管壁中的血液动力学力，以响应动脉粥样硬化刺激。过去十年的研究揭示了 microRNAs（miRNAs）在调节内皮细胞（ECs）、血管平滑肌细胞（VSMCs）、巨噬细胞和脂质稳态中的多种病理生理效应和信号通路中的关键作用，这些在动脉粥样硬化病变形成中至关重要。这些 miRNAs 的表达要么是对生物力学（流动反应）刺激的反应，要么是对生化（非流动反应）刺激的反应。最近的证据也表明长链非编码 RNA（lncRNAs）在介导几种动脉粥样硬化过程中起着重要作用。在这篇综述中，我们详细总结了 miRNA 依赖性调节的当前范例，lncRNAs 在动脉粥样硬化的发生和进展中的新兴作用，以及针对这些的临床干预，试图为动脉粥样硬化开发新的诊断和治疗方法。
