Modification of Chemical and Physical Properties of Lipoproteins by Probucol in Type IIa Hypercholesterolemia

抄録

Probucol, a lipid-lowering drug, is transported in plasma primarily in the lipoproteins, mainly low density lipoproteins (LDL). This study examines the effect of probucol on the physical and chemical properties of LDL and high density lipoproteins (HDL) in three groups of subjects: 14 healthy normolipidemic subjects (control group), 15 untreated patients with type IIa hyperlipoproteinemia (HC group), and 16 patients treated with probucol 500mg twice daily (HC-Prob group). The lipoprotein fluidity parameters (fluorescence anisotropy and flow activation energy) were assessed by diphenyl hexatriene (DPH) fluorescence polarization. Compared with control group lipoproteins, untreated HC group LDL exhibited a lower triglyceride content and a significantly higher cholesteryl ester (CE) to triglyceride (TG) ratio. There was no difference in HDL chemical composition between the two groups. DPH fluorescence anisotropy and flow activation energy were significantly increased in both LDL and HDL from untreated hypercholesterolemic patients. Major modifications in the chemical composition and physical properties of lipoproteins were noted after probucol treatment. The triglyceride content was increased and the CE/TG ratio was decreased in both LDL and HDL. DPH fluorescence anisotropy and flow activation energy were significantly lower in LDL and HDL from treated HC patients than in those from untreated patients. Lipoproteins from the HC-Prob group were found to have the same fluidity parameters as the control group particles. The modifications of physical and chemical properties of LDL and HDL after the drug treatment can be related to the presence of probucol inside of the lipoprotein particles, which modifications in turn lead to alterations in the structure and metabolic behavior of the particles.