HDL biology
Probucol significantly raises CETP activity while shrinking large LDL and both HDL subfractions (Artery 1993)
Original title: Decrease of plasma large, light LDL (LDL1), HDL2 and HDL3 levels with concomitant increase of cholesteryl ester transfer protein (CETP) activity by probucol in type II hyperlipoproteinemia
The effects of 12 weeks of probucol treatment on plasma lipoprotein subfractions and LCAT and CETP activities were studied in type II hyperlipoproteinemia. Probucol did not change VLDL-triglyceride, apoB, apoCII, or apoCIII, but slightly reduced VLDL and IDL cholesterol. Large, light LDL1 cholesterol, phospholipid, and apoB fell significantly (28.5%, 18.1%, and 23.3%, all P<0.01 or better) while LDL1 triglyceride was unchanged, and gel electrophoresis confirmed diminished large LDL. Probucol markedly reduced HDL2 cholesterol, triglyceride, phospholipid, and apoA-I (36.2%, 25.8%, 34.4%, 35.6%, all P<0.01 or better) and reduced HDL3 cholesterol, phospholipid, and apoA-I (17.4%, 18.3%, 19.8%, all P<0.01), with HDL2 falling more than HDL3. LCAT activity was unchanged, but CETP activity rose significantly from 126.6 to 172.8 units after 12 weeks (P<0.001). The authors conclude probucol decreases LDL1, HDL2, and HDL3 while making them triglyceride-rich, alongside increased CETP activity.
Original abstract
The effects of 12 week probucol treatment on plasma lipoprotein subfraction levels and on lecithin: cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) activities in type II hyperlipoproteinemia were investigated. Plasma VLDL-TG, VLDL-apoB, VLDL-apoCII and VLDL-apoCIII concentrations were not changed by probucol, but VLDL-TC and VLDL-PL levels were slightly reduced. Probucol slightly reduced plasma IDL-TC, but not IDL-TG, IDL-PL and IDL-apoB levels. Plasma large, light LDL (LDL1)-TC, LDL1-PL, LDL1-apoB levels were decreased significantly by 28.5 +/- 20.1% (p < 0.001), 18.1 +/- 18.8% (p < 0.01) and 23.3 +/- 19.1% (p < 0.001) by probucol treatment while LDL1-TG concentration was unchanged. Absolute amounts of plasma small, heavy LDL(LDL2)-TC, LDL2-TG, LDL2-PL and LDL2-apoB levels remained unchanged but percent increases of LDL2-TC and LDL2-apoB were statistically significant (p < 0.05). 2-16% gradient polyacrylamide gel electrophoresis demonstrated the diminution of LDL of large size by probucol treatment. Probucol markedly reduced plasma high density lipoprotein levels. The reductions of HDL2-TC, HDL2-TG, HDL2-PL and HDL2-apoAI concentrations were 36.2 +/- 25.4% (p < 0.001), 25.8 +/- 36.9% (p < 0.01), 34.4 +/- 23.8% (p < 0.001) and 35.6 +/- 28.4% (p < 0.001). Probucol significantly decreased plasma HDL3-TC, HDL3-PL and HDL3-apoAI amounts by 17.4 +/- 22.9% (p < 0.01), 18.3 +/- 20.8% (p < 0.01) and 19.8 +/- 27.9% (p < 0.01) without change of HDL3-TG level. The decrease of HDL2 level was more marked than that of HDL3 level. Probucol did not change LCAT activities. Probucol significantly stimulated CETP activities from 126.6 +/- 50.6 units to 172.8 +/- 40.2 units by 12 week treatment (p < 0.001). We concluded that probucol decreased plasma LDL1, HDL2 and HDL3 amounts and made them triglyceride-rich with the concomitant increase of CETP activities.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.