Neutrophil microvesicles drive atherosclerosis by delivering miR-155 to atheroprone endothelium

Gomez, Ingrid; Ward, Ben; Souilhol, Céline; Recarti, Chiara; Ariaans, Mark; Johnston, Jessica; Burnett, Amanda; Mahmoud, Marwa; Luong, Le Anh; West, Laura E.; Long, Merete B.; Parry, Siôn A; Woods, Rachel; Hulston, Carl J.; Benedikter, Birke J.; Niespolo, Chiara; Bazaz, Rohit; Francis, Sheila; Kiss-Tóth, Endre; Zandvoort, Marc van; Schober, Andreas; Hellewell, Paul G.; Evans, Paul C.; Ridger, Victoria

doi:10.1038/s41467-019-14043-y

Cited by 110 publications

(109 citation statements)

References 63 publications

(69 reference statements)

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“…Cellular senescence for example contributes to agedependent changes in circulating extracellular vesicle cargo 46 . Moreover, the differential loading of vesicles is correlated to different human diseases [47][48][49] . Likewise, for the cellular part, resolution can be increased.…”

Section: Discussionmentioning

confidence: 99%

Common diseases alter the physiological age-related blood microRNA profile

et al. 2020

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Aging is a key risk factor for chronic diseases of the elderly. MicroRNAs regulate post-transcriptional gene silencing through base-pair binding on their target mRNAs. We identified nonlinear changes in age-related microRNAs by analyzing whole blood from 1334 healthy individuals. We observed a larger influence of the age as compared to the sex and provide evidence for a shift to the 5’ mature form of miRNAs in healthy aging. The addition of 3059 diseased patients uncovered pan-disease and disease-specific alterations in aging profiles. Disease biomarker sets for all diseases were different between young and old patients. Computational deconvolution of whole-blood miRNAs into blood cell types suggests that cell intrinsic gene expression changes may impart greater significance than cell abundance changes to the whole blood miRNA profile. Altogether, these data provide a foundation for understanding the relationship between healthy aging and disease, and for the development of age-specific disease biomarkers.

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Section: Discussionmentioning

confidence: 99%

Common diseases alter the physiological age-related blood microRNA profile

et al. 2020

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“…This indicated that miR-155 promoted and Bmal1 hindered the progression of atherosclerosis. According to Gomez et al, exosomes carrying miR-155 released from neutrophils during vascular infiltration were fused with ECs, leading to vascular inflammation and atherosclerosis (24). Faccini et al also indicated the high diagnostic value of miR-155 in coronary atherosclerosis (25).…”

Section: Discussionmentioning

confidence: 99%

miR‑155 induces endothelial cell apoptosis and inflammatory response in atherosclerosis by regulating Bmal1

Liang

Zhang

et al. 2020

Exp Ther Med

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Atherosclerosis is the leading cause of death from vascular diseases worldwide, and endothelial cell (EC) dysfunction is the key cause of atherosclerosis. miR-155 was found to induce endothelial injury and to trigger atherosclerosis. In addition, brain and muscle ARNT-like protein-1 (Bmal1) has been found to be closely related to EC function. Therefore, the present study aimed to explore the mechanism underlying the regulation of Bmal1 by miR-155 in the induction of EC apoptosis and inflammatory response in atherosclerosis. The atherosclerosis model in apolipoprotein E (ApoE)-/mice was established. miR-155 and Bmal1 expression was quantified by RT-qPCR and western blot analysis, respectively. The role of miR-155 and Bmal1 in atherosclerosis was evaluated through changes in cardiac function, plaque area, cardiomyocyte apoptosis, and inflammatory factor levels in mice. Moreover, the regulatory relationship between them was identified by dual-luciferase reporter gene assay to explore the mechanism of action of miR-155. After the modeling, the expression of miR-155 was upregulated and Bmal1 was downregulated in aorta, and there was a significant linear correlation between them. Upregulation of miR-155 increased the atherosclerotic plaque area, cell apoptosis, total cholesterol (TC) and triglyceride (TG), as well as weakened aortic diastolic function. However, opposite changes occurred after downregulation of miR-155 or an increase in Bmal1. In addition, the microRNA. org website predicted that there were targeted binding sites between miR-155 and Bmal1, which was verified with a dual-luciferase reporter gene assay. miR-155 was able to inhibit the expression by targeting Bmal1. Moreover, a rescue experiment showed that Bmal1 hindered the promotion of miR-155 in regards to atherosclerosis. In conclusion, miR-155 induces EC apoptosis and inflammatory response, weakens aortic diastolic function, and promotes the progression of atherosclerosis through targeted inhibition of Bmal1.

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“…Reduced neutrophil migratory accuracy and reduced bacterial killing has been identified in hyperglycaemia and replicated in vitro following neutrophil exposure to serum from diabetic patients [78]. In vitro, neutrophils have also been implicated in cell-to-cell crosstalk, with neutrophil microvesicles associated with inducing classical pathological changes in diabetic cardiovascular pathology [79] and COPD [80]. Furthermore, age-related changes seen in the muscle (e.g.…”

Section: Theme 1: Accelerated Ageing In Multimorbiditymentioning

confidence: 97%

Shared mechanisms of multimorbidity in COPD, atherosclerosis and type-2 diabetes: the neutrophil as a potential inflammatory target

2020

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Multimorbidity is increasingly common and current healthcare strategies are not always aligned to treat this complex burden of disease. COPD, type-2 diabetes mellitus (T2D) and cardiovascular disease, especially atherosclerosis, occur more frequently together than expected, even when risk factors such as smoking, obesity, inactivity and poverty are considered. This supports the possibility of unifying mechanisms that contribute to the pathogenesis or progression of each condition.Neutrophilic inflammation is causally associated with COPD, and increasingly recognised in the pathogenesis of atherosclerosis and T2D, potentially forming an aetiological link between conditions. This link might reflect an overspill of inflammation from one affected organ into the systemic circulation, exposing all organs to an increased milieu of proinflammatory cytokines. Additionally, increasing evidence supports the involvement of other processes in chronic disease pathogenesis, such as cellular senescence or changes in cellular phenotypes.This review explores the current scientific evidence for inflammation, cellular ageing and cellular processes, such as reactive oxygen species production and phenotypic changes in the pathogenesis of COPD, T2D and atherosclerosis; highlighting common mechanisms shared across these diseases. We identify emerging therapeutic approaches that target these areas, but also where more work is still required to improve our understanding of the underlying cellular biology in a multimorbid disease setting.

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Neutrophil microvesicles drive atherosclerosis by delivering miR-155 to atheroprone endothelium

Cited by 110 publications

References 63 publications

Common diseases alter the physiological age-related blood microRNA profile

Common diseases alter the physiological age-related blood microRNA profile

miR‑155 induces endothelial cell apoptosis and inflammatory response in atherosclerosis by regulating Bmal1

Shared mechanisms of multimorbidity in COPD, atherosclerosis and type-2 diabetes: the neutrophil as a potential inflammatory target

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