Fenofibrate reduces lipoprotein associated phospholipase A2 mass and oxidative lipids in hypertriglyceridemic subjects with the metabolic syndrome - 09/08/11
Résumé |
Background |
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a macrophage-synthesized lipase that is primarily bound to small electronegative low-density lipoproteins (LDLs). Lipoprotein-associated phospholipase A2 oxidatively modifies LDL and generates the proinflammatory byproducts oxidized fatty acids (ox-FAs) and lysophosphatidylcholine. Fenofibrate reduces Lp-PLA2 mass; however, it remains unknown whether the anti-inflammatory effects of fenofibrate are related to changes in LDL subclasses.
Methods |
This was a randomized, double-blind, controlled clinical trial designed to investigate the effects of 3-month treatment with fenofibrate (160 mg/d) on Lp-PLA2 mass, LDL subclasses, and ox-FAs among 55 hypertriglyceridemic (≥1.7 and <6.78 mmol/L) subjects with the metabolic syndrome.
Results |
Fenofibrate treatment lowered fasting Lp-PLA2 mass by 13.2% (−19.0 to −7.7) versus placebo (2.3% [−5.0 to 4.1], P = .0002) and total ox-FA by 15.5% (−34.2 to +1.4) versus an 11.5% increase with placebo (P = .0013). In age-, sex-, and treatment-adjusted models, changes in Lp-PLA2 mass were associated with reductions in chemical LDL cholesterol (r = 0.59, P < .01) and measured total LDL particles (LDL-Ps) (r = 0.64, P < .01) and small LDL-Ps (r = 0.57, P < .01). In models that included small LDL, effects of fenofibrate on Lp-PLA2 mass were attenuated (P = .125), but not in models that included LDL cholesterol (P < .0001) and LDL-Ps (P = .005). Changes in Lp-PLA2 mass were not significantly associated with changes in ox-FA or inflammatory markers.
Conclusions |
Among hypertriglyceridemic subjects with the metabolic syndrome, fenofibrate therapy reduced Lp-PLA2 mass, and these changes were associated with fewer small LDL-Ps.
Le texte complet de cet article est disponible en PDF.Abbreviations : [3H]-PAF, DIACOR, FIELD, HDL-C, HRP, ICAM-1, IQR, LDL, LDL-C, LDL-P, Lp-PLA2, lysoPC, MCP-1, MIP-1α, NF-κB, NMR, ox-FA, oxLDL, ox-NEFA, PPARα, TMB, VCAM-1
Plan
| This study was supported through a research grant to the University of Michigan and Northwestern University from Abbott Laboratories, Inc. DiaDexus, Inc, provided analyses of lipoprotein associated phospholipase A2 mass for this study. Dr Rosenson has received funds from Abbott Laboratories, Inc (Abbott Park, IL) (research grant, speaker's bureau, honoraria payment), and LipoScience, Inc (Raleigh, NC) (speaker's bureau, honoraria payment, ownership interest, and consultant/advisory board). |
Vol 155 - N° 3
P. 499.e9-499.e16 - mars 2008 Retour au numéro
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