Emerging Roles of Extracellular Vesicle-Delivered Circular RNAs in Atherosclerosis

Abstract

Atherosclerosis (AS) is universally defined as chronic vascular inflammation induced by dyslipidaemia, obesity, hypertension, diabetes and other risk factors. Extracellular vesicles as information transmitters regulate intracellular interactions and their important cargo circular RNAs are involved in the pathological process of AS. In this review, we summarize the current data to elucidate the emerging roles of extracellular vesicle-derived circular RNAs (EV-circRNAs) in AS and the mechanism by which EV-circRNAs affect the development of AS. Additionally, we discuss their vital role in the progression from risk factors to AS and highlight their great potential for use as diagnostic biomarkers of and novel therapeutic strategies for AS.

Plasma Pattern of Extracellular Vesicles Isolated from Hepatitis C Virus Patients and Their Effects on Human Vascular Endothelial Cells

“…Hence, infectious agents could induce host cells to release EVs, which, in turn, could provide a long-lasting feedback loop to either exacerbate the infection, local and systemic inflammation, and endothelial dysfunction also at distant sites [ 24 , 39 ], suggesting a mechanistic role of EVs at the intersection of inflammatory processes and CVD [ 24 ]. Coming back to the specific context of hepatitis C, this could be crucial not only as regards the well-known damage of EVs on the liver—primarily due to their role in mediating immune response evasion and progressive fibrosis development—[ 40 , 41 ], but also concerning some of the aforementioned extrahepatic manifestations most linked to atherosclerosis and/or coagulation activation, although this still deserves further confirmation at least in patients with mild to moderate liver disease [ 42 , 43 , 44 ]. Furthermore, this could be an explanation for why the detrimental effect induced by HCV infection can persist over time well after the end of the acute phase or viral eradication [ 19 , 45 ].…”

Epigenetic modifications in obesity‐associated diseases

“…87 CircRNAs derived from extracellular vesicles can also elevate the risk of hypertension and atherosclerosis by modulating blood lipids, lipid deposition, and endothelial cell function. 199 Evidence shows that ncRNAs have significant biological functions and participate in forming complex gene regulatory networks. Exosomes assist in transporting ncRNAs to distant organs, amplifying the negative effects of AT.…”

“…Mechanistically, circRNAs can competitively bind to miRNAs to regulate the expression of genes associated with coronary artery disease 87 . CircRNAs derived from extracellular vesicles can also elevate the risk of hypertension and atherosclerosis by modulating blood lipids, lipid deposition, and endothelial cell function 199 …”

Extracellular vesicles in atherosclerosis and vascular calcification: the versatile non-coding RNAs from endothelial cells and vascular smooth muscle cells

“…CircRNAs have been identified in the process of AS, such as circ_USP36, circ_0007478, circCHFR, and circ_0001879 ( 219 – 223 ). CircRNAs encapsulated in EVs were also involved in the process of AS ( 224 ). CircNPHP4 in monocyte-EVs regulated heterogeneous adhesion in coronary heart atherosclerotic disease by the modulation of miR-1231 ( 225 ).…”