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 language | English (US) |
|---|---|
| Pages (from-to) | 1054-1064 |
| Number of pages | 11 |
| Journal | Circulation Research |
| Volume | 111 |
| Issue number | 8 |
| DOIs | |
| State | Published - Sep 2012 |
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Keywords
- atherosclerosis
- endothelial dysfunction
- fatty acids
- hypertriglyceridemia
- triglycerides
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
Cite this
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 journal › Article
}
TY - JOUR
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
Y1 - 2012/9
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
UR - http://www.scopus.com/inward/record.url?scp=84867026573&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867026573&partnerID=8YFLogxK
U2 - 10.1161/CIRCRESAHA.112.270314
DO - 10.1161/CIRCRESAHA.112.270314
M3 - Article
C2 - 22874466
AN - SCOPUS:84867026573
VL - 111
SP - 1054
EP - 1064
JO - Circulation Research
JF - Circulation Research
SN - 0009-7330
IS - 8
ER -