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

Chongxiu Sun, Kenan Alkhoury, Ying I. Wang, Greg A. Foster, Christopher E. Radecke, Kayan Tam, Christina M. Edwards, Marc T. Facciotti, Ehrin J. Armstrong, Anne A Knowlton, John W. Newman, Anthony G. Passerini, Scott I. Simon

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Rationale: 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. Objective:: 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. Methods and Results: 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-α 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. Ω3-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. Conclusions:: 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.

Original languageEnglish (US)
Pages (from-to)1054-1064
Number of pages11
JournalCirculation Research
Volume111
Issue number8
DOIs
StatePublished - Sep 2012

Fingerprint

Interferon Regulatory Factor-1
Vascular Cell Adhesion Molecule-1
Lipoproteins
Meals
Triglycerides
Fats
MicroRNAs
Intercellular Adhesion Molecule-1
Unsaturated Fatty Acids
Endothelium
Monocytes
Endothelial Cells
Apolipoprotein C-III
E-Selectin
Hypertriglyceridemia
High Fat Diet
Apolipoproteins E
Nonesterified Fatty Acids
Atherosclerosis
Anti-Inflammatory Agents

Keywords

  • atherosclerosis
  • endothelial dysfunction
  • fatty acids
  • hypertriglyceridemia
  • triglycerides

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Sun, C., Alkhoury, K., Wang, Y. I., Foster, G. A., Radecke, C. E., Tam, K., ... Simon, S. I. (2012). IRF-1 and miRNA126 modulate VCAM-1 expression in response to a high-fat meal. Circulation Research, 111(8), 1054-1064. https://doi.org/10.1161/CIRCRESAHA.112.270314

IRF-1 and miRNA126 modulate VCAM-1 expression in response to a high-fat meal. / Sun, Chongxiu; Alkhoury, Kenan; Wang, Ying I.; Foster, Greg A.; Radecke, Christopher E.; Tam, Kayan; Edwards, Christina M.; Facciotti, Marc T.; Armstrong, Ehrin J.; Knowlton, Anne A; Newman, John W.; Passerini, Anthony G.; Simon, Scott I.

In: Circulation Research, Vol. 111, No. 8, 09.2012, p. 1054-1064.

Research output: Contribution to journalArticle

Sun, C, Alkhoury, K, Wang, YI, Foster, GA, Radecke, CE, Tam, K, Edwards, CM, Facciotti, MT, Armstrong, EJ, Knowlton, AA, Newman, JW, Passerini, AG & Simon, SI 2012, 'IRF-1 and miRNA126 modulate VCAM-1 expression in response to a high-fat meal', Circulation Research, vol. 111, no. 8, pp. 1054-1064. https://doi.org/10.1161/CIRCRESAHA.112.270314
Sun C, Alkhoury K, Wang YI, Foster GA, Radecke CE, Tam K et al. IRF-1 and miRNA126 modulate VCAM-1 expression in response to a high-fat meal. Circulation Research. 2012 Sep;111(8):1054-1064. https://doi.org/10.1161/CIRCRESAHA.112.270314
Sun, Chongxiu ; Alkhoury, Kenan ; Wang, Ying I. ; Foster, Greg A. ; Radecke, Christopher E. ; Tam, Kayan ; Edwards, Christina M. ; Facciotti, Marc T. ; Armstrong, Ehrin J. ; Knowlton, Anne A ; Newman, John W. ; Passerini, Anthony G. ; Simon, Scott I. / IRF-1 and miRNA126 modulate VCAM-1 expression in response to a high-fat meal. In: Circulation Research. 2012 ; Vol. 111, No. 8. pp. 1054-1064.
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abstract = "Rationale: 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. Objective:: 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. Methods and Results: 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-α 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. Ω3-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. Conclusions:: 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.",
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author = "Chongxiu Sun and Kenan Alkhoury and Wang, {Ying I.} and Foster, {Greg A.} and Radecke, {Christopher E.} and Kayan Tam and Edwards, {Christina M.} and Facciotti, {Marc T.} and Armstrong, {Ehrin J.} and Knowlton, {Anne A} and Newman, {John W.} and Passerini, {Anthony G.} and Simon, {Scott I.}",
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T1 - IRF-1 and miRNA126 modulate VCAM-1 expression in response to a high-fat meal

AU - Sun, Chongxiu

AU - Alkhoury, Kenan

AU - Wang, Ying I.

AU - Foster, Greg A.

AU - Radecke, Christopher E.

AU - Tam, Kayan

AU - Edwards, Christina M.

AU - Facciotti, Marc T.

AU - Armstrong, Ehrin J.

AU - Knowlton, Anne A

AU - Newman, John W.

AU - Passerini, Anthony G.

AU - Simon, Scott I.

PY - 2012/9

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N2 - Rationale: 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. Objective:: 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. Methods and Results: 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-α 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. Ω3-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. Conclusions:: 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.

AB - Rationale: 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. Objective:: 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. Methods and Results: 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-α 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. Ω3-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. Conclusions:: 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.

KW - atherosclerosis

KW - endothelial dysfunction

KW - fatty acids

KW - hypertriglyceridemia

KW - triglycerides

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