Abstract
BackgroundThe association between modulation of detailed lipoprotein profiles and cholesterol ester transfer (CET) activity by peroxisome proliferator-activated receptor (PPAR)-a agonists in patients with coronary artery disease remains unclear. We assessed lipid profiles, plasma CET activity, and in-stent intimal hyperplasia after fenofibrate treatment in patients who underwent elective coronary stenting.MethodsForty-three consecutive patients who underwent elective coronary stenting were randomized to the fenofibrate group (300 mg/day for 25 weeks, n = 22) or the control group (n = 21). At baseline and follow up, CET activity and lipoprotein profiles were measured, and quantitative coronary angiography was performed.ResultsIn the fenofibrate group, the levels of large very low-density lipoprotein cholesterol, and small low-density lipoprotein (LDL) cholesterol decreased and those of small high-density lipoprotein (HDL) cholesterol increased. Besides, CET activity decreased independent of the effect of fenofibrate on total and LDL cholesterol. The reduction of CET activity significantly correlated with the increase in LDL particle size (r = 0.47, P = 0.03) and the decrease of triglycerides in large HDL subclasses (r = 0.48, P = 0.03). Although there were no significant differences in restenosis parameters between the two groups, low CET activity significantly correlated with the inhibition of neointimal hyperplasia (r = 0.56, P = 0.01).ConclusionsFenofibrate inhibited CET activity and thereby improved atherogenic lipoprotein profiles, and reduced intimal hyperplasia after coronary stenting.
Highlights
The association between modulation of detailed lipoprotein profiles and cholesterol ester transfer (CET) activity by peroxisome proliferator-activated receptor (PPAR)-a agonists in patients with coronary artery disease remains unclear
There were no significant differences in age, gender, body mass index (BMI), lipid profiles, HbA1c, hsCRP, CET activity, prevalence of diabetes mellitus and hypertension, and smoking history between the two groups at baseline
CET activity decreased by 30.5% in the fenofibrate group (P < 0.05) but it remained unchanged in the control group
Summary
The association between modulation of detailed lipoprotein profiles and cholesterol ester transfer (CET) activity by peroxisome proliferator-activated receptor (PPAR)-a agonists in patients with coronary artery disease remains unclear. Fibrates, which act as peroxisome proliferator-activated receptor (PPAR)-a agonists, are widely used in the treatment of atherogenic dyslipidemia. These drugs reduce triglycerides, raise high-density lipoprotein (HDL) cholesterol, and improve the small, dense low-density lipoprotein (LDL) phenotype [1]. CETP inhibition results in an increase of anti-inflammatory and anti-oxidative properties of HDL conferred by apoA-1, paraoxonase 1 and platelet activating factoracetylhydrolase [9,10,11] These findings suggest CETP inhibition could be the target of treatment to prevent atherosclerotic diseases. The association between modulation of lipoproteins and CET activity by fenofibrate regarding the initiation and progression of atherosclerosis remains unclear
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