miR-186-5p Dysregulation in Serum Exosomes from Patients with AMI Aggravates Atherosclerosis via Targeting LOX-1

Abstract

Purpose The formation of macrophage-derived foam cells via the uptake of modified lipoproteins is a pivotal development event in atherosclerosis. It has been reported that clinical and experimental myocardial infarction could accelerate atherosclerosis. Several studies have suggested the critical role of exosomes in cardiovascular diseases. However, the role of exosomes from patients with acute myocardial infarction (AMI) patients in atherogenesis remains unclear. Patients and Methods Serum exosomes from AMI patients (AMI-Exo) and control individuals (Con-Exo) were isolated and characterized. These exosomes were studied in vitro and in vivo to determine their impact on macrophage foaming and atherogenesis. Results Our results showed that AMI-Exo promoted foam cell formation in oxidized low-density lipoprotein (ox-LDL)-treated macrophages and progression of atherosclerosis in high-fat/cholesterol diet-fed ApoE −/− mice together with a significantly upregulated levels of lectin-like ox-LDL receptor-1 (LOX-1). The miR-186-5p was found to be downregulated in AMI-Exo and macrophages administered with AMI-Exo. Moreover, serum exosomal miR-186-5p achieved high diagnostic performance for AMI. Luciferase reporter assay indicated that miR-186-5p directly inhibited LOX-1. The endogenous or exogenous miR-186-5p deficiency enhanced lipid accumulation by upregulating LOX-1, whereas miR-186-5p mimics had a reverse effect. Conclusion In conclusion, the current findings suggest that dysregulated miR-186-5p in AMI-Exo may explain the contribution of acute ischemia events to the advancement of atherosclerosis by enhancing macrophage foaming via its target, LOX-1.

Longitudinal change of serum exosomal miR-186-5p estimates major adverse cardiac events in acute myocardial infarction patients receiving percutaneous coronary intervention

“…In this research, it was discovered that serum exosomal miR-186-5p was increased in AMI patients receiving PCI vs. HCs. A potential explanation might be that exosomal miR-186-5p might modulate the LOX-1 and SHIP2-mediated PI3K/AKT/mTOR pathways to facilitate lipid accumulation and promote viability and invasion in VSMCs, thereby contributing to atherosclerosis, which led to the occurrence of AMI ( 15 , 17 ). Therefore, serum exosomal miR-186-5p reflected an increased risk of AMI.…”

“…Of note, exosomal miR, such as miR-21-3p, miR-182-5p, and miR-27b-3p, plays a fundamental role in atherogenesis, which is responsible for the pathology and progression of cardiovascular diseases ( 11 – 14 ). Regarding miR-186-5p, a previous study indicates that serum exosomal miR-186-5p shows a good diagnostic performance for AMI, and its dysregulation in exosomes contributes to atherosclerosis by targeting lectin-like ox-LDL receptor-1 (LOX-1) ( 15 ). Additionally, another study reports that serum exosomal miR-186-5p is positively associated with lipid level, coronary stenosis degree, and MACE risk in coronary heart disease patients ( 16 ).…”

Extracellular vesicles derived from CD4+ T cells carry DGKK to promote sepsis-induced lung injury by regulating oxidative stress and inflammation

“…The EVs derived from the above-mentioned CD4 + T cells and serum were isolated and purified in accordance with a previously described method with some modifications [ 27 ]. Briefly, the serum samples, which were thawed in a water bath at 25 °C and placed on ice, and conditioned medium of CD4 + T cells with or without LPS treatment, were harvested and centrifuged at 4 °C at 2000 × g for 10 min.…”

Exosomes: Diagnostic and Therapeutic Implications in Cancer

“…Exosomes are present in culture supernatants, serum, plasma, urine, and various other sources [ 7 ]. They contain DNA, miRNAs, long non-coding RNAs (lnc RNAs), circulatory RNAs (circ RNAs), DNA fragments, proteins, and various lipids [ 8 , 9 , 10 ].…”