Post-prandial endothelial dysfunction in hypertriglyceridemic subjects: molecular mechanisms and gene expression studies.
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 8h 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-alpha in human endothelial cells and increased the DNA binding activity of CREB, NFAT and NF-kappaB. 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.


CONCLUSIONS
These effects may relate to the severe impairment of endothelial function seen during the post-prandial phase in hypertriglyceridemic patients.
Norata
Giuseppe Danilo
GD
Department of Pharmacological Sciences, University of Milan,Via Balzaretti 9, 20133 Milan, Italy. Danilo.Norata@unimi.it
Grigore
Liliana
L
Raselli
Sara
S
Redaelli
Laura
L
Hamsten
Anders
A
Maggi
Franco
F
Eriksson
Per
P
Catapano
Alberico Luigi
AL
D000328:Adult; D002784:Cholesterol / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects*; D015870:Gene Expression; D006801:Humans; D006953:Hyperlipoproteinemia Type IV / Q000235:genetics / Q000503:physiopathology*; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D015398:Signal Transduction; D014280:Triglycerides / Q000378:metabolism; D014652:Vascular Diseases / Q000235:genetics* / Q000503:physiopathology*
D004041:Dietary Fats; D014280:Triglycerides; D002784:Cholesterol