Effects of fenofibrate on endothelial function and cell adhesion molecules during post-prandial lipemia in hypertriglyceridemia.
BACKGROUND
Fasting and post-prandial hypertriglyceridemia have been associated with endothelial dysfunction.


OBJECTIVE
To investigate the effects of a 3-month treatment with fenofibrate (200 mg daily) on endothelial reactivity and inflammatory state in hypertriglyceridemic patients at fast and after an oral fat load.


METHODS
Brachial flow-mediated vasodilation (FMV) and the circulating levels of intercellular adhesion molecule (ICAM) and vascular cellular adhesion molecule (VCAM) were determined in 10 hypertriglyceridemic patients.


RESULTS
Before treatment, post-prandial phase was characterized by an increase in triglycerides (3.7 +/- 1 mmol/L at baseline vs. 4.2 +/- 1, 6.5 +/- 1, 6.6 +/- 2, and 5.3 +/- 2 mmol/L after 2, 4, 6, and 8 h), a decrease in FMV (4.3 +/- 2% at baseline vs. 2.8 +/- 1, 2.2 +/- 1, and 1.3 +/- 1% after 2, 4, and 6 h), and an increase in ICAM and VCAM. After fenofibrate there was a significant reduction in fasting triglycerides (3.7 +/- 1.3 vs. 2.1 +/- 0.8 mmol/L), ICAM (480 +/- 113 vs. 269 +/- 65 ng/mL) and VCAM (1821 +/- 570 vs. 1104 +/- 376 ng/mL), and an increase in FMV (4.3 +/- 2 vs. 7.1 +/- 2%). Post-prandially triglycerides increased (2.1 +/- 1 at baseline vs. 2.4 +/- 2 and 3.6 +/- 1 mmol/L after 4 and 6 h), FMV decreased (7.1 +/- 2 at baseline vs. 5.8 +/- 2, 5.5 +/- 2, 5.9 +/- 2, 6.4 +/- 2% after 2, 4, 6, and 8 h), and there was an increase of ICAM and VCAM. Before therapy post-prandial changes in FMV had an inverse correlation with the changes in triglycerides (r = -0.34; P < 0.05) and ICAM (r = -0.66; P < 0.001).


CONCLUSIONS
The transient endothelial dysfunction observed in hypertriglyceridemic subjects during post-prandial lipemia is mediated by post-prandial triglyceride increase and by the activation of inflammatory response. The anti-inflammatory activity of fenofibrate may represent an additional mechanism of its favorable action on the endothelial function during fasting and the post-prandial phase.
Marchesi
S
S
Unit of Internal Medicine, Angiology and Atherosclerosis, University of Perugia, Perugia, Italy. simonamarchesi@yahoo.it
Lupattelli
G
G
Lombardini
R
R
Roscini
A R
AR
Siepi
D
D
Vaudo
G
G
Pirro
M
M
Sinzinger
H
H
Schillaci
G
G
Mannarino
E
E
D000328:Adult; D015815:Cell Adhesion Molecules / Q000097:blood*; D004041:Dietary Fats / Q000097:blood*; D004730:Endothelium, Vascular / Q000187:drug effects; D005215:Fasting / Q000097:blood*; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D015228:Hypertriglyceridemia / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
D015815:Cell Adhesion Molecules; D004041:Dietary Fats; D000960:Hypolipidemic Agents; D011345:Fenofibrate