Effects of fenofibrate on endothelial function and cell adhesion molecules during post-prandial lipemia in hypertriglyceridemia

Marchesi, Simona; Lupattelli, Graziana; Lombardini, Rita; Roscini, Anna Rita; Siepi, Donatella; Vaudo, Gaetano; Pirro, Matteo; Sinzinger, H.; Schillaci, Giuseppe; Mannarino, Elmo

doi:10.1046/j.0269-4727.2003.00512.x

Cited by 45 publications

(32 citation statements)

References 26 publications

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“…Our laboratory and others have found higher circulating sICAM-1 and sVCAM-1 in obese compared with normal weight adolescents (Desideri et al 2005;O'Brien et al 2006). Previous investigations have consistently shown increases in sICAM-1 and sVCAM-1 in diabetic and hypertriglyceridemic populations following an OFTT (Ceriello et al 2004;Marchesi et al 2003;Nappo et al 2002), suggesting increased endothelial cell activation in an already pro-atherosclerotic environment. In contrast, only small increases (Ceriello et al 2004;Nappo et al 2002), or no changes (Gill et al 2003a;Tsai et al 2004), have been observed in postprandial sICAM-1 and sVCAM-1 in healthy subjects.…”

Section: Discussionmentioning

confidence: 94%

Effect of prior exercise on postprandial lipemia and markers of inflammation and endothelial activation in normal weight and overweight adolescent boys

et al. 2009

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Postprandial lipemia (PPL) is associated with impaired endothelial function and inflammation. Acute exercise reduces PPL in adults. This investigation examined the effect of an acute bout of exercise on postprandial changes in triglycerides (TG), glucose, insulin, inflammation [white blood cell count (WBC), interleukin-6 (IL-6) tumor necrosis factor-alpha, C-reactive protein (CRP)] and endothelial activation [soluble intercellular adhesion molecule-1 (sICAM-1), vascular adhesion molecule-1 (sVCAM-1)] following a high-fat meal in adolescents. Ten normal weight (NW) (BMI, 20.9 +/- 1.7 kg m(-2); 15.6 +/- 0.7 years) and eight overweight (OW) (BMI, 28.3 +/- 3.6 kg m(-2); 15.9 +/- 0.4 years) adolescent boys underwent two 6-h oral fat tolerance tests (OFTT) separated by 7-10 days. On the evening prior to each OFTT, subjects either rested or completed a treadmill exercise bout (65% V(O)(2max); 600 kcal expended). Exercise reduced (P < 0.01) the postprandial TG area under the curve by approximately 20% in the NW and OW groups. The postprandial glucose and insulin response did not differ between the control and exercise trials or between the NW and OW groups. Circulating leukocytes and plasma IL-6 levels increased (P < 0.01) in the NW and OW groups 6 h following the OFTT in both experimental conditions. There were no changes in CRP, sVCAM-1 or sICAM-1 following the OFTT and there were no differences between experimental condition or NW and OW groups. In conclusion, a moderate exercise bout prior to a high-fat meal effectively reduces postprandial TG concentrations to a similar degree in both NW and OW adolescents, but does not reduce the concomitant postprandial increase in WBC or IL-6.

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Section: Discussionmentioning

confidence: 94%

Effect of prior exercise on postprandial lipemia and markers of inflammation and endothelial activation in normal weight and overweight adolescent boys

et al. 2009

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“…It has been shown both in vitro [46] and in vivo [47] that fibrates modulate monocyte recruitment by limiting the expression of leucocyte adhesion molecules on the surface of both endothelial cells and infiltrating mononuclear cells. Moreover, PPARα agonists reduce the release of matrix metalloproteinases by monocyte/macrophages [48]. Direct anti-atherogenic actions of PPARα agonists at the vascular wall [49] seem to be mediated by a reduction in the expression of inflammatory genes regulated by NF-κB [50][51][52].Finally, treatment with fibrates can improve FMD via regulating the balance between vasodilation and vasoconstriction.…”

Section: Discussionmentioning

confidence: 99%

Fibrate therapy and flow-mediated dilation: A systematic review and meta-analysis of randomized placebo-controlled trials

Sahebkar

Giua

Pedone

et al. 2016

Pharmacological Research

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Flow-mediated dilation (FMD) of the brachial artery reflects endothelium-dependent vasodilator function; since it correlates with coronary endothelial function, its reduction could predict cardiovascular events. Several studies have investigated the potential impact of fibrates therapy on endothelial function, but clinical findings have not been fully consistent. We aimed to conduct a meta-analysis of randomized placebo-controlled trials in order to clarify whether fibrate therapy could improve endothelial function. A systematic search in PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases was performed to identify randomized placebo-controlled trials investigating the effect of fibrates on endothelial function as estimated by FMD. A randomeffects model and generic inverse variance method were used for meta-analysis. Sensitivity analysis, risk of bias evaluation, and publication bias assessment were carried out using standard methods. Random-effects meta-regression was used to evaluate the impact of treatment duration on the estimated effect size. Fifteen trials with a total of 556 subjects met the eligibility criteria. Fibrate 3 therapy significantly improves FMD (weighted mean difference [WMD]: 1.64%, 95% CI: 1.15, 2.13, p < 0.001) and the result was confirmed in both subgroups with treatment durations ≤8 weeks (WMD: 1.35%, 95% CI: 0.85, 1.86, p < 0.001) and >8 weeks (WMD: 2.55%, 95% CI: 1.21, 3.89, p < 0.001). When the analysis was stratified according to the fibrate type, a significant effect was observed with fenofibrate but not with gemfibrozil, though difference between the two subgroups was not significant. Meta-analysis of data from trials where nitrate mediated dilation (NMD) was available did not suggest a significant change in NMD following treatment with fibrates. The results of this meta-analysis suggest that fibrates may exert beneficial effects on endothelial function, even over a short-term treatment course.

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“…29 We and others found that fenofibrate therapy significantly improved flow-mediated dilation ( Figure 1). 13,14,30 Plausible mechanisms for this include beneficial changes in lipoprotein levels. In support of this hypothesis, significant correlations between improvement in flow-mediated dilation and changes in total cholesterol, LDL cholesterol, and non-HDL cholesterol levels were observed.…”

Section: Effects On Vasomotor Functionmentioning

confidence: 99%

Beneficial Vascular and Metabolic Effects of Peroxisome Proliferator-Activated Receptor-α Activators

Han¹,

Quon²,

Koh³

2005

Hypertension

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Abstract-Fibric acid is a synthetic ligand of the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-␣ that is highly expressed in skeletal muscle and heart, where it promotes ␤-oxidation of fatty acids to mediate hypolipidemic actions. PPAR-␣ regulates expression of key proteins involved in atherogenesis, vascular inflammation, plaque instability, and thrombosis. Thus, PPAR-␣ may exert direct antiatherogenic actions in the vascular wall. Endothelial dysfunction associated with the metabolic syndrome and other insulin-resistant states is characterized by impaired insulin-stimulated nitric oxide production from the endothelium and decreased blood flow to skeletal muscle. Thus, improvement in insulin sensitivity leads to improved endothelial function. This may be an additional mechanism whereby fibrates decrease the incidence of coronary heart disease. Adiponectin is a protein secreted specifically by adipose cells that may couple regulation of insulin sensitivity with energy metabolism and serve to link obesity with insulin resistance. In this review, we discuss the mechanisms underlying the vascular and metabolic effects of fibrates that may act synergistically to prevent or regress atherosclerosis and coronary heart disease.

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Effects of fenofibrate on endothelial function and cell adhesion molecules during post-prandial lipemia in hypertriglyceridemia

Cited by 45 publications

References 26 publications

Effect of prior exercise on postprandial lipemia and markers of inflammation and endothelial activation in normal weight and overweight adolescent boys

Effect of prior exercise on postprandial lipemia and markers of inflammation and endothelial activation in normal weight and overweight adolescent boys

Fibrate therapy and flow-mediated dilation: A systematic review and meta-analysis of randomized placebo-controlled trials

Beneficial Vascular and Metabolic Effects of Peroxisome Proliferator-Activated Receptor-α Activators

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