MicroRNA-mediated mechanisms of the cellular stress response in atherosclerosis

Abstract

| 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. Schober, A. et al. Nat. Rev. Cardiol. advance online publication 7

Circulating Plasma Extracellular Microvesicle MicroRNA Cargo and Endothelial Dysfunction in Children with Obstructive Sleep Apnea

“…Here, we found that fluorescently labeled exosomes were internalized into endothelial cells (see Figure E3), where they could be implicated in a myriad of important processes (39)(40)(41)(42)(43)(44). Based on the selectivity of miRNA loading into extracellular vesicles (EV) and their stability (45), potential differences in miRNA exosomal cargo were identified, and were compatible with previous work implicating exosomal miRNAs not only in angiogenesis and other vascular phenomena (46,47), while also suggesting the possibility that exosomes may provide therapeutic opportunities (48). We recently assessed the biomarker capabilities of plasma miRNAs (19), and our findings support the driving assumption that a cluster of circulating miRNAs may reliably discern between children with ED and children with NEF.…”

Extracellular Ribonucleic Acids (RNA) Enter the Stage in Cardiovascular Disease

“…47,48 A contribution of different eRNA species is emerging as critical mediators of these mechanisms that control (ischemic) cardiovascular disease. As recent reviews have specifically concentrated on various aspects of miRNAs in this context, [12][13][14][15] these issues will not be dealt with here in detail.…”

“…It should be noted, however, that in many cases, we currently do not yet understand whether certain types of eRNA, structural prerequisites, or specific nucleotide sequences of the RNA are required to exert their functions, which is an uncertainty embodied by the rather unspecific term eRNA. The function of miRNAs in this context has been reviewed elsewhere [12][13][14][15] and will not be discussed in detail.…”

CXCL16 in Vascular Pathology Research: from Macro Effects to microRNAs

“…Cardiovascular diseases are among them. Because there are already thorough reviews that summarize current knowledge about miRs implicated in atherosclerosis susceptibility, development, and progression [81][82][83][84][85][86][87][88] , we will focus on the part of atherosclerosis pathology where different miRs could potentially alter vascular physiology by the direct or indirect regulation of CXCL16 gene expression.…”