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IRF-1 and miRNA126 modulate VCAM-1 expression in response to a high-fat meal.

ABSTRACT: A high-fat diet accompanied by hypertriglyceridemia increases an individual's risk for development of atherosclerosis. An early event in this process is monocyte recruitment through binding to vascular cell adhesion molecule 1 (VCAM-1) upregulated on inflamed arterial endothelium. Diets high in polyunsaturated fatty acids (PUFAs) may provide athero-protection by ameliorating this effect.We investigated the acute regulation of VCAM-1 expression in human aortic endothelial cells (HAEC) in response to triglyceride-rich lipoproteins (TGRL) isolated from subjects after consumption of a high-fat meal.Postprandial TGRL isolated from 38 subjects were categorized as proatherogenic or antiatherogenic according to their capacity to alter the inflammatory response of HAEC. Proatherogenic TGRL increased expression of VCAM-1, intercellular adhesion molecule 1 (ICAM-1), and E-selectin by ?20% compared with stimulation with tumor necrosis factor-? alone, whereas antiatherogenic TGRL decreased VCAM-1 expression by ?20% while still upregulating ICAM-1. The relative atherogenicity of TGRL positively correlated with particle density of TG, apolipoprotein (Apo)CIII, ApoE, and cholesterol. ?3-PUFA mimicked the effect of antiatherogenic TGRL by downregulating VCAM-1 expression. TGRL exerted this differential regulation of VCAM-1 by reciprocally modulating expression and activity of the transcription factor interferon regulatory factor 1 (IRF-1) and expression of microRNA 126 (miR-126). Overexpression or silencing of IRF-1 or miR-126 expression recapitulated the proatherogenic or antiatherogenic regulation of VCAM-1.In response to a high-fat meal, TGRL bias the inflammatory response of endothelium via transcriptional and posttranscriptional editing of VCAM-1. Subjects with an anti-inflammatory response to a meal produced TGRL that was enriched in nonesterified fatty acids, decreased IRF-1 expression, increased miR-126 activity, and diminished monocyte arrest.

SUBMITTER: Sun C

PROVIDER: S-EPMC3810165 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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IRF-1 and miRNA126 modulate VCAM-1 expression in response to a high-fat meal.

Sun Chongxiu C Alkhoury Kenan K Wang Ying I YI Foster Greg A GA Radecke Christopher E CE Tam Kayan K Edwards Christina M CM Facciotti Marc T MT Armstrong Ehrin J EJ Knowlton Anne A AA Newman John W JW Passerini Anthony G AG Simon Scott I SI

Circulation research 20120808 8

<h4>Rationale</h4>A high-fat diet accompanied by hypertriglyceridemia increases an individual's risk for development of atherosclerosis. An early event in this process is monocyte recruitment through binding to vascular cell adhesion molecule 1 (VCAM-1) upregulated on inflamed arterial endothelium. Diets high in polyunsaturated fatty acids (PUFAs) may provide athero-protection by ameliorating this effect.<h4>Objective</h4>We investigated the acute regulation of VCAM-1 expression in human aortic ...[more]

PMID: 22874466

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Project description:BackgroundDyslipidemia is a feature of impaired metabolic health in conjunction with impaired glucose metabolism and central obesity. However, the contribution of factors to postprandial lipemia in healthy but metabolically at-risk adults is not well understood. We investigated the collective contribution of several physiologic and lifestyle factors to postprandial triglyceride (TG) response to a high-fat meal in healthy, overweight and obese adults.MethodsOverweight and obese adults (n = 35) underwent a high-fat meal challenge with blood sampled at fasting and hourly in the 4-hour postprandial period after a breakfast containing 50 g fat. Incremental area under the curve (iAUC) and postprandial magnitude for TG were calculated and data analyzed using a linear model with physiologic and lifestyle characteristics as explanatory variables. Model reduction was used to assess which explanatory variables contributed most to the postprandial TG response.ResultsTG responses to a high-fat meal were variable between individuals, with approximately 57 % of participants exceeded the nonfasting threshold for hypertriglyceridemia. Visceral adiposity was the strongest predictor of TG iAUC (β = 0.53, p = 0.01), followed by aerobic exercise frequency (β = 0.31, p = 0.05), insulin resistance based on HOMA-IR (β = 0.30, p = 0.04), and relative exercise intensity at which substrate utilization crossover occurred (β = 0.05, p = 0.04). For postprandial TG magnitude, visceral adiposity was a strong predictor (β = 0.43, p < 0.001) followed by aerobic exercise frequency (β = 0.23, p = 0.01), and exercise intensity for substrate utilization crossover (β = 0.53, p = 0.01).ConclusionsPostprandial TG responses to a high-fat meal was partially explained by several physiologic and lifestyle characteristics, including visceral adiposity, insulin resistance, aerobic exercise frequency, and relative substrate utilization crossover during exercise.Trial registrationClinicalTrials.gov, NCT04128839 , Registered 16 October 2019 - Retrospectively registered.

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IRF-1 and miRNA126 modulate VCAM-1 expression in response to a high-fat meal.

Publications

IRF-1 and miRNA126 modulate VCAM-1 expression in response to a high-fat meal.

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