Abstract 12669: Effect of Probucol on Antioxidant Properties of HDL in Patients with Heterozygous Familial Hypercholesterolemia
Objectives-High density lipoprotein (HDL) has multi-antiatherogenic functions such as antioxidation, anti-inflammation and anticoagulation, in addition to a key mediator of reverse cholesterol transport. Probucol, known as a lipid lowering drug, is also a potent antioxidant, but it decreases serum HDL-cholesterol (HDL-C) levels. To elucidate the effect of probucol on antioxidant properties of HDL, we investigated the function of HDL derived from patients with heterozygous familial hypercholesterolemia (FH) who have been treated with probucol.
Methods and Results-Probucol-treated FH patients (n=21) showed a 47% reduction of serum HDL-C levels compared to probucol-untreated FH patients (n=15), although there was no significant difference in LDL-cholesterol (LDL-C) levels. High performance liquid chromatography (HPLC) analysis revealed that probucol diminished HDL particle size compared to non-treated group. Antioxidant capacity of HDL was evaluated by the effect to protect reference LDL from oxidation that was induced in the presence of an oxidizing agent, AAPH. The HDL derived from probucol-treated group demonstrated a significantly prolonged time to start oxidation (lag phase duration) by 112%, decreased maximum oxidation rate by 14%, and lowered maximum concentration of conjugated dienes (CD) formation by 15%. Furthermore, HDL-associated paraoxonase 1 (PON1) activity, but not platelet-activating factor acetyl-hydrolase (PAF-AH) correlated with lag phase duration, and inversely correlated with maximal oxidation rate and maximal CD concentration in AAPH-induced LDL oxidation.
Conclusion-Probucol reduces HDL-C levels and HDL particle size in patients with heterozygous FH, while it concomitantly enhances the anti-oxidative properties of HDL possibly through increasing PON1 activity.
- © 2011 by American Heart Association, Inc.