HDL activates expression of genes stimulating cholesterol efflux in human monocyte-derived macrophages

Orekhov, Alexander N.; Pushkarsky, Tatiana; Oishi, Yumiko; Nikiforov, Nikita G.; Zhelankin, Andrey V.; Dubrovsky, Larisa; Makeev, Vsevolod J.; Foxx, Kathy; Jin, Xueting; Kruth, Howard S.; Собенин, И.А.; Sukhorukov, Vasily N.; Zakiev, Emile; Kontush, Anatol; Goff, Wilfried Le; Bukrinsky, Michael

doi:10.1016/j.yexmp.2018.08.003

Cited by 13 publications

(7 citation statements)

References 53 publications

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“…Also, miR-1277-5p and miR-1273c have been reported as altered in inflammatory statuses ( Zalewski et al, 2020 ). Altogether, the observed anti-correlations between cholesterol intake and these miRNAs suggest that cholesterol itself could participate in the regulation of its efflux in macrophages, as recently reported for HDL ( Orekhov et al, 2018 ).…”

Section: Discussionsupporting

confidence: 80%

Intake of Natural Compounds and Circulating microRNA Expression Levels: Their Relationship Investigated in Healthy Subjects With Different Dietary Habits

et al. 2021

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Diet has a strong influence on many physiological processes, which in turn have important implications on a variety of pathological conditions. In this respect, microRNAs (miRNAs), a class of small non-coding RNAs playing a relevant epigenetic role in controlling gene expression, may represent mediators between the dietary intake and the healthy status. Despite great advances in the field of nutri-epigenomics, it remains unclear how miRNA expression is modulated by the diet and, specifically, the intake of specific nutrients. We investigated the whole circulating miRNome by small RNA-sequencing performed on plasma samples of 120 healthy volunteers with different dietary habits (vegans, vegetarians, and omnivores). Dietary intakes of specific nutrients were estimated for each subject from the information reported in the food-frequency questionnaire previously validated in the EPIC study. We focused hereby on the intake of 23 natural compounds (NCs) of the classes of lipids, micro-elements, and vitamins. We identified 78 significant correlations (rho > 0.300, p-value < 0.05) among the estimated daily intake of 13 NCs and the expression levels of 58 plasma miRNAs. Overall, vitamin D, sodium, and vitamin E correlated with the largest number of miRNAs. All the identified correlations were consistent among the three dietary groups and 22 of them were confirmed as significant (p-value < 0.05) by age-, gender-, and body-mass index-adjusted Generalized Linear regression Model analysis. miR-23a-3p expression levels were related with different NCs including a significant positive correlation with sodium (rho = 0.377) and significant negative correlations with lipid-related NCs and vitamin E. Conversely, the estimated intake of vitamin D was negatively correlated with the expression of the highest number of circulating miRNAs, particularly miR-1277-5p (rho = −0.393) and miR-144-3p (rho = −0.393). Functional analysis of the targets of sodium intake-correlated miRNAs highlighted terms related to cardiac development. A similar approach on targets of those miRNAs correlated with vitamin D intake showed an enrichment in genes involved in hormone metabolisms, while the response to chronic inflammation was among the top enriched processes involving targets of miRNAs negatively related with vitamin E intake. Our findings show that nutrients through the habitual diet influence circulating miRNA profiles and highlight that this aspect must be considered in the nutri-epigenomic research.

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Section: Discussionsupporting

confidence: 80%

Intake of Natural Compounds and Circulating microRNA Expression Levels: Their Relationship Investigated in Healthy Subjects With Different Dietary Habits

et al. 2021

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“…Macrophages enter the intima, Ω(t), by the chemotaxis of MCP-1 [31] and become foam cells by the uptake of oxidized LDL [27]. On the other hand, HDL removes the cholesterol from foam cells [25] which become M2 macrophages transfer back to the liver, referred to as the RCT process [23]. Then we model the density of macrophages, M, below:…”

Section: Mathematical Modelmentioning

confidence: 99%

Bifurcation analysis of a free boundary model of plaque formation associated with the cholesterol ratio

Hao,

Zheng

2020

Preprint

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The low-density lipoprotein (LDL)/high-density lipoprotein (HDL)-cholesterol ratio has been shown a high correlation with the cardiovascular risk assessment. Is it possible to quantify the correlation mathematically? In this paper, we develop a bifurcation analysis for a mathematical model of the plaque formation with a free boundary in the early stage of atherosclerosis. This bifurcation analysis, to the ratio of LDL/HDL, is based on the explicit formulation of radially symmetric steady-state solutions. By performing the perturbation analysis to these solutions, we establish the existence of bifurcation branches and derive a theoretical condition that a bifurcation occurs for different modes. Then we also analyze the stability of radially symmetric steady-state solutions and conduct numerical simulations to verify all the theoretical results.

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“…Recently, we analyzed the transcriptome of HDL-treated monocyte-derived macrophages in order to identify genes that could be upregulated by HDL (Orekhov et al, 2018c). Only three identified genes were significantly up-regulated by HDL-treatment: fatty acid desaturase 1 (FADS1, regulates unsaturation of fatty acids), insulin induced gene 1 (INSIG1, regulates lipid synthesis), and the low-density lipoprotein receptor (LDLR, binds non-modified LDL).…”

Section: Monocyte Activatability and Lipid Profilementioning

confidence: 99%

Trained Circulating Monocytes in Atherosclerosis: Ex Vivo Model Approach

et al. 2019

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Inflammation is one of the key processes in the pathogenesis of atherosclerosis. Numerous studies are focused on the local inflammatory processes associated with atherosclerotic plaque initiation and progression. However, changes in the activation state of circulating monocytes, the main components of the innate immunity, may precede the local events. In this article, we discuss tolerance, which results in decreased ability of monocytes to be activated by pathogens and other stimuli, and training, the ability of monocyte to potentiate the response to pathological stimuli, and their relation to atherosclerosis. We also present previously unpublished results of the experiments that our group performed with monocytes/macrophages isolated from atherosclerosis patients. Our data allow assuming the existence of relationship between the formation of monocyte training and the degree of atherosclerosis progression. The suppression of trained immunity ex vivo seems to be a perspective model for searching anti-atherogenic drugs.

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HDL activates expression of genes stimulating cholesterol efflux in human monocyte-derived macrophages

Cited by 13 publications

References 53 publications

Intake of Natural Compounds and Circulating microRNA Expression Levels: Their Relationship Investigated in Healthy Subjects With Different Dietary Habits

Intake of Natural Compounds and Circulating microRNA Expression Levels: Their Relationship Investigated in Healthy Subjects With Different Dietary Habits

Bifurcation analysis of a free boundary model of plaque formation associated with the cholesterol ratio

Trained Circulating Monocytes in Atherosclerosis: Ex Vivo Model Approach

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