Post-prandial endothelial dysfunction in hypertriglyceridemic subjects: Molecular mechanisms and gene expression studies

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• 作者：Giuseppe Danilo Norata ; Liliana Grigore ; Sara Raselli ; Laura Redaelli ; Anders Hamsten ; Franco Maggi ; Per Eriksson ; Alberico Luigi Catapano
• 关键词：Post-prandial lipoproteins ; Gene expression ; Endothelial dysfunction ; Inflammation
• 刊名：Atherosclerosis
• 出版年：2007
• 期刊代码：28_00219150
• 类别：med
• 出版时间：August 2007
• 卷：193
• 期：2
• 页码：321-327
• 文件大小：1015 K

摘要

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.