TY - JOUR
T1 - Post-prandial endothelial dysfunction in hypertriglyceridemic subjects
T2 - Molecular mechanisms and gene expression studies
AU - Norata, Giuseppe Danilo
AU - Grigore, Liliana
AU - Raselli, Sara
AU - Redaelli, Laura
AU - Hamsten, Anders
AU - Maggi, Franco
AU - Eriksson, Per
AU - Catapano, Alberico Luigi
PY - 2007/8
Y1 - 2007/8
N2 - Objective: Triglyceride-rich lipoproteins (TGRLs) are a cardiovascular risk factor and induce endothelial dysfunction. In the present study, we investigated the effects of post-prandial TGRLs from type IV hyperlipidemic subjects on endothelial activation addressing the effects of the lipoproteins on intracellular pathways and gene expression. Methods: Thirty fasted hypertriglyceridemic patients were given an oral fat load (OFL) and blood samples were collected before the OFL (T0) and 2, 4, 6 and 8 h thereafter. Endothelial function, determined as flow-mediated dilatation of the brachial artery, was assessed at the same time points. TGRLs were isolated at T0 and T4 (PP-TGRL) for in vitro studies. Results: Compared with TGRLs, PP-TGRLs induced to a larger extent phosphorylation of p38 MAPK, CREB and IKB-α in human endothelial cells and increased the DNA binding activity of CREB, NFAT and NF-κB. Furthermore, PP-TRGLs upregulated the expression of several pro-inflammatory genes including vascular cell adhesion molecule-1 (VCAM-1), PECAM-1, ELAM-1, intercellular adhesion molecule-1 (ICAM-1), P-selectin, MCP-1, interleukin-6 (IL-6), TLR-4, CD40, ADAMTS1 and PAI-1. Conclusion: These effects may relate to the severe impairment of endothelial function seen during the post-prandial phase in hypertriglyceridemic patients.
AB - Objective: Triglyceride-rich lipoproteins (TGRLs) are a cardiovascular risk factor and induce endothelial dysfunction. In the present study, we investigated the effects of post-prandial TGRLs from type IV hyperlipidemic subjects on endothelial activation addressing the effects of the lipoproteins on intracellular pathways and gene expression. Methods: Thirty fasted hypertriglyceridemic patients were given an oral fat load (OFL) and blood samples were collected before the OFL (T0) and 2, 4, 6 and 8 h thereafter. Endothelial function, determined as flow-mediated dilatation of the brachial artery, was assessed at the same time points. TGRLs were isolated at T0 and T4 (PP-TGRL) for in vitro studies. Results: Compared with TGRLs, PP-TGRLs induced to a larger extent phosphorylation of p38 MAPK, CREB and IKB-α in human endothelial cells and increased the DNA binding activity of CREB, NFAT and NF-κB. Furthermore, PP-TRGLs upregulated the expression of several pro-inflammatory genes including vascular cell adhesion molecule-1 (VCAM-1), PECAM-1, ELAM-1, intercellular adhesion molecule-1 (ICAM-1), P-selectin, MCP-1, interleukin-6 (IL-6), TLR-4, CD40, ADAMTS1 and PAI-1. Conclusion: These effects may relate to the severe impairment of endothelial function seen during the post-prandial phase in hypertriglyceridemic patients.
KW - Endothelial dysfunction
KW - Gene expression
KW - Inflammation
KW - Post-prandial lipoproteins
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U2 - 10.1016/j.atherosclerosis.2006.09.015
DO - 10.1016/j.atherosclerosis.2006.09.015
M3 - Article
C2 - 17055512
AN - SCOPUS:34249297789
VL - 193
SP - 321
EP - 327
JO - Atherosclerosis
JF - Atherosclerosis
SN - 0021-9150
IS - 2
ER -