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

Giuseppe Danilo Norata, Liliana Grigore, Sara Raselli, Laura Redaelli, Anders Hamsten, Franco Maggi, Per Eriksson, Alberico Luigi Catapano

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)321-327
Number of pages7
JournalAtherosclerosis
Volume193
Issue number2
DOIs
Publication statusPublished - Aug 2007

Keywords

  • Endothelial dysfunction
  • Gene expression
  • Inflammation
  • Post-prandial lipoproteins

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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