Toronto General Research Institute, University Health Network Toronto, ON, Canada ; Department of Laboratory Medicine and Pathobiology, University of Toronto Toronto, ON, Canada ; Heart and Stroke/Richard Lewar Centre of Excellence in Cardiovascular Research Toronto, ON, Canada.
Front Genet. 2014 Dec 10;5:422. doi: 10.3389/fgene.2014.00422. eCollection 2014.
Cardiovascular diseases such as atherosclerosis are one of the leading causes of morbidity and mortality worldwide. The clinical manifestations of atherosclerosis, which include heart attack and stroke, occur several decades after initiation of the disease and become more severe with age. Inflammation of blood vessels plays a prominent role in atherogenesis. Activation of the endothelium by inflammatory mediators leads to the recruitment of circulating inflammatory cells, which drives atherosclerotic plaque formation and progression. Inflammatory signaling within the endothelium is driven predominantly by the pro-inflammatory transcription factor, NF-κB. Interestingly, activation of NF-κB is enhanced during the normal aging process and this may contribute to the development of cardiovascular disease. Importantly, studies utilizing mouse models of vascular inflammation and atherosclerosis are uncovering a network of noncoding RNAs, particularly microRNAs, which impinge on the NF-κB signaling pathway. Here we summarize the literature regarding the control of vascular inflammation by microRNAs, and provide insight into how these microRNA-based pathways might be harnessed for therapeutic treatment of disease. We also discuss emerging areas of endothelial cell biology, including the involvement of long noncoding RNAs and circulating microRNAs in the control of vascular inflammation.
心血管疾病，如动脉粥样硬化，是全球发病率和死亡率的主要原因之一。动脉粥样硬化的临床表现，包括心脏病发作和中风，在疾病开始后几十年才出现，并随着年龄的增长而变得更加严重。血管炎症在动脉粥样硬化形成中起着突出的作用。炎症介质激活内皮细胞，导致循环炎症细胞的募集，从而驱动动脉粥样硬化斑块的形成和进展。内皮细胞内的炎症信号主要由促炎转录因子 NF-κB 驱动。有趣的是，NF-κB 的激活在正常衰老过程中增强，这可能导致心血管疾病的发生。重要的是，利用血管炎症和动脉粥样硬化的小鼠模型进行的研究揭示了一个非编码 RNA 网络，特别是 microRNAs，它们影响 NF-κB 信号通路。在这里，我们总结了 microRNAs 对血管炎症的控制的文献，并深入探讨了如何利用这些基于 microRNA 的途径来治疗疾病。我们还讨论了内皮细胞生物学的新兴领域，包括长链非编码 RNA 和循环 microRNAs 在血管炎症控制中的参与。
