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  • Title: Probucol treatment in hypercholesterolemic patients: effects on lipoprotein composition, HDL particle size, and cholesteryl ester transfer.
    Author: Bagdade JD, Kaufman D, Ritter MC, Subbaiah PV.
    Journal: Atherosclerosis; 1990 Oct; 84(2-3):145-54. PubMed ID: 2282096.
    Abstract:
    Despite probucol's capacity to induce regression of tendinous xanthomata and reduce whole plasma and LDL cholesterol (LDL-C) in patients with hypercholesterolemia, its therapeutic use in the United States has been limited because of concern about its HDL-lowering effects. To assess the possibility that probucol might facilitate mobilization of tissue cholesterol in the presence of low HDL levels as a consequence of favorable changes in lipoprotein composition and function, we have analyzed lipoproteins and studied cholesteryl ester transfer (CET) in hypercholesterolemic patients before and after treatment. Prior to treatment, the free cholesterol (FC)/lecithin (L) ratio in plasma, a new index of cardiovascular risk, and the mass of cholesteryl ester transferred from HDL to the apo B-containing lipoproteins (CET) both were significantly increased (P less than 0.001). As previously shown, plasma cholesterol, LDL-C, HDL-C, HDL2, and apolipoproteins A-I, A-II, and B all fell significantly following probucol treatment. The FC/L ratio in plasma (P less than 0.01) and HDL2 (P less than 0.01) both fell significantly also, as did the sphingomyelin/lecithin ratio in VLDL + LDL (P less than 0.001) which is typically increased in untreated patients with hypercholesterolemia. Nondenaturing gradient gel electrophoresis in 6 patients revealed that the quantitative changes in HDL were associated with a redistribution of particles characterized by a decrease in the prevalence of the largest (HDL2b) and a relative increase in the number of the smallest (HDL3b) particles. Moreover, CET following probucol therapy returned to levels which were indistinguishable from those of normolipidemic controls. These results indicate that untreated patients with hypercholesterolemia have abnormalities in (1) lipoprotein composition which have been shown to retard the movement of cholesterol from tissues to HDL, and in (2) CET which is accelerated and can potentially lead to the formation in plasma of atherogenic CE-enriched apo B-containing lipoproteins. Probucol's capacity to reverse these specific alterations suggests that it may have beneficial effects on cholesterol transport in patients with hypercholesterolemia.
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