Non-coding RNA regulation of endothelial and macrophage functions during atherosclerosis

Abstract

The endothelial lining can be viewed as the first line of defense against risk factors of vascular disease. Endothelial dysfunction is regarded as an initial event for atherogenesis since defects in vascular integrity and homeostasis are responsible for lipid infiltration and recruitment of monocytes into the vessel wall. Monocytes-turned-macrophages, which possess astounding inflammatory plasticity, perpetuate chronic inflammation and growth of atherosclerotic plaques and, are therefore central for the pathogenesis of atherosclerosis. Because endothelial cells and macrophages are key players during atherogenesis, it is crucial to understand the regulation of their functions in order to develop strategies to intervene disease progression. Interestingly, non-coding RNAs (ncRNAs), broad class of RNA molecules that do not code for proteins, are capable of reprogramming multiple cell functions and, thus, can be used as target agents. MicroRNAs are small ncRNAs whose roles in the regulation of vascular functions and development of atherosclerosis through post-transcriptional manipulation of gene expression have been widely explored. Recently, other ncRNAs including long noncoding RNAs (lncRNAs) have also emerged as potential regulators of these functions. However, given their poor-genetic conservation between species, much work will be needed to elucidate the specific role of lncRNAs in vascular biology. This review aims to provide a comprehensive perspective of ncRNA, mostly focusing in lncRNAs, mechanism of action and relevance in regulating lipid metabolism-independent endothelial and macrophages functions in the pathogenesis of atherosclerosis.

Keywords: Atherosclerosis; endothelial cells; lncRNAs; macrophages; miRNAs; noncoding RNAs.