Transcoronary gradients of HDL-associated MicroRNAs in unstable coronary artery disease

Choteau, Sébastien A.; Torres, Luisa; Barraclough, J.; Elder, A.; Martínez, Gonzalo; Fan, William Y. Chen; Shrestha, Sudichhya; Barter, Philip J.; Celermajer, David S.; Rye, Kerry‐Anne; Patel, Sanjay; Tabet, Fatiha

doi:10.1016/j.ijcard.2017.09.190

Cited by 18 publications

(11 citation statements)

References 35 publications

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“…This may be attributed to the following possible reasons: (1) the subjects enrolled were Han individuals from mainland China (Asian) in our study, and Japan (Asian) in the study of Mamoru et al [14], but Ireland (European) for study of O Sullivan et al [15] The difference in miR-16 expression in CAD may be associated with the ethnic difference; (2) the difference in stable and unstable CAD. The upregulation of miR-16 in stable CAD may be a protective response [15,21]; (3) the sample size of these studies, including ours, was not large.…”

Section: Discussionmentioning

confidence: 90%

Overexpression of MicroRNA-16 Alleviates Atherosclerosis by Inhibition of Inflammatory Pathways

Wang

Cai

et al. 2020

BioMed Research International

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Background. Our previous study demonstrated that the expression of miR-16 was downregulated in the cell and animal models of atherosclerosis (AS), a main contributor to coronary artery disease (CAD). Overexpression of miR-16 inhibited the formation of foam cells by exerting anti-inflammatory roles. These findings indicated miR-16 may be an anti-atherogenic and CAD miRNA. The goal of this study was to further validate the expression of miR-16 in CAD patients and explore its therapeutic roles in an AS animal model. Methods. A total of 40 CAD patients and 40 non-CAD people were prospectively registered in our study. The AS model was established in ApoE-/- mice fed a high-fat diet. The model mice were randomly treated with miR-16 agomiR (n=10) or miR-negative control (n=10). Hematoxylin-eosin staining was conducted for histopathological examination in thoracic aorta samples. ELISA and immunohistochemistry were performed to determine the expression levels of inflammatory factors (IL-6, TNF-α, MCP-1, IL-1β, IL-10, and TGF-β). qRT-PCR and western blotting were carried out to detect the mRNA and protein expression levels of PDCD4, miR-16, and mitogen-activated protein kinase pathway-related genes. Results. Compared with the normal control, miR-16 was downregulated in the plasma and peripheral blood mononuclear cell of CAD patients, and its expression level was negatively associated with IL-6 and the severity of CAD evaluated by the Gensini score, but positively related with IL-10. Injection of miR-16 agomiR in ApoE-/- mice reduced the formation of atherosclerotic plaque and suppressed the accumulation of proinflammatory factors (IL-6, TNF-α, MCP-1, and IL-1β) in the plasma and tissues but promoted the secretion of anti-inflammatory factors (IL-10 and TGF-β). Mechanism analysis showed overexpression of miR-16 might downregulate target mRNA PDCD4 and then activate p38 and ERK1/2, but inactivate the JNK pathway. Conclusions. Our findings suggest miR-16 may be a potential diagnostic biomarker and therapeutic target for atherosclerotic CAD.

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Section: Discussionmentioning

confidence: 90%

Overexpression of MicroRNA-16 Alleviates Atherosclerosis by Inhibition of Inflammatory Pathways

Wang

Cai

et al. 2020

BioMed Research International

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“…At an epigenetic level, the presence of co-morbidities has also been shown to induce changes to the HDL-miRNA signature [60]. As such, an association between HDL-miRNAs profile and CAD stability has been established [97], and the content of HDL-miR-223 is found to be altered in the presence of insulin resistance and familial hypercholesterolemia subjects [26,[98][99][100][101][102]. Extending these previous findings, we have recently evidenced that hypercholesterolemic HDL particles transport higher levels of miR-126 as compared to native-HDL, which in turn is delivered to endothelial cells through an SRB1-dependent mechanism likely modulating HIF-1α expression [103].…”

Section: Impact Of Cardiovascular Risk Factor and Co-morbidities On Hmentioning

confidence: 99%

Advances in HDL: Much More than Lipid Transporters

Ben‐Aicha

Badimon

Vilahur

2020

IJMS

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High Density Lipoprotein (HDL) particles, beyond serving as lipid transporters and playing a key role in reverse cholesterol transport, carry a highly variable number of proteins, micro-RNAs, vitamins, and hormones, which endow them with the ability to mediate a plethora of cellular and molecular mechanisms that promote cardiovascular health. It is becoming increasingly evident, however, that the presence of cardiovascular risk factors and co-morbidities alters HDLs cargo and protective functions. This concept has led to the notion that metrics other than HDL-cholesterol levels, such as HDL functionality and composition, may better capture HDL cardiovascular protection. On the other hand, the potential of HDL as natural delivery carriers has also fostered the design of engineered HDL-mimetics aiming to improve HDL efficacy or as drug-delivery agents with therapeutic potential. In this paper, we first provide an overview of the molecules known to be transported by HDL particles and mainly discuss their functions in the cardiovascular system. Second, we describe the impact of cardiovascular risk factors and co-morbidities on HDL remodeling. Finally, we review the currently developed HDL-based approaches.

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“…MicroRNA-223 is potentially atheroprotective in patients with ACS. 47 It prevents pro-inflammatory polarization of macrophages 48 and inhibits NLRP3 assembly in monocytes 49 as well as reducing endothelial expression of ICAM-1. 50 In our study, we found reduced circulating expression of miR-223 in ACS standard therapy plus colchicine patients compared to patients with ACS, suggesting uptake into inflammatory cells to reduce NLRP3 assembly and subsequent cytokine release consistent with previous work by our group.…”

Section: Differences In Mirna Expression Between Colchicine Treated Amentioning

confidence: 99%

A MicroRNA Signature in Acute Coronary Syndrome Patients and Modulation by Colchicine

Barraclough

Joglekar

Januszewski

et al. 2020

J Cardiovasc Pharmacol Ther

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Background: Circulating microRNAs (miRNAs) may play a pathogenic role in acute coronary syndromes (ACS). It is not yet known if miRNAs dysregulated in ACS are modulated by colchicine. We profiled miRNAs in plasma samples simultaneously collected from the aorta, coronary sinus, and right atrium in patients with ACS. Methods: A total of 396 of 754 miRNAs were detected by TaqMan real-time polymerase chain reaction from EDTA-plasma in a discovery cohort of 15 patients (n = 3 controls, n = 6 ACS standard therapy, n = 6 ACS standard therapy plus colchicine). Fifty-one significantly different miRNAs were then measured in a verification cohort of 92 patients (n = 13 controls, n = 40 ACS standard therapy, n = 39 ACS standard therapy plus colchicine). Samples were simultaneously obtained from the coronary sinus, aortic root, and right atrium. Results: Circulating levels of 30 of 51 measured miRNAs were higher in ACS standard therapy patients compared to controls. In patients with ACS, levels of 12 miRNAs (miR-17, -106b-3p, -191, -106a, -146a, -130a, -223, -484, -889, -425-3p, -629, -142-5p) were lower with colchicine treatment. Levels of 7 of these 12 miRNA were higher in ACS standard therapy patients compared to controls and returned to levels seen in control individuals after colchicine treatment. Three miRNAs suppressed by colchicine (miR-146a, miR-17, miR-130a) were identified as regulators of inflammatory pathways. MicroRNAs were comparable across sampling sites with select differences in the transcoronary gradient of 4 miRNA. Conclusion: The levels of specific miRNAs elevated in ACS returned to levels similar to control individuals following colchicine. These miRNAs may mediate ACS (via inflammatory pathways) or increase post-ACS risk, and could be potentially used as biomarkers of treatment efficacy.

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Transcoronary gradients of HDL-associated MicroRNAs in unstable coronary artery disease

Cited by 18 publications

References 35 publications

Overexpression of MicroRNA-16 Alleviates Atherosclerosis by Inhibition of Inflammatory Pathways

Overexpression of MicroRNA-16 Alleviates Atherosclerosis by Inhibition of Inflammatory Pathways

Advances in HDL: Much More than Lipid Transporters

A MicroRNA Signature in Acute Coronary Syndrome Patients and Modulation by Colchicine

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