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.
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.
authors.affiliation: Department of Internal Medicine, Tokai University Oiso Hospital, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Homma
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.forename: H
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: H
authors.initials: H
authors.lastname: Sakane
authors.forename: H
authors.initials: H
authors.lastname: Ozawa
authors.forename: M
authors.initials: M
authors.lastname: Matsuda
authors.forename: Y
authors.initials: Y
authors.lastname: Mikami
authors.forename: Y
authors.initials: Y
authors.lastname: Mikami
authors.forename: H
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D002352:Carrier Proteins / Q000097:blood*; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000097:blood*; D006023:Glycoproteins; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy*; D008075:Lipoproteins, HDL / Q000097:blood* / Q000737:chemistry; D008077:Lipoproteins, LDL / Q000097:blood* / Q000737:chemistry; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood; D010743:Phospholipids / Q000097:blood; D011341:Probucol / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
chemical_list: C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D006023:Glycoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010743:Phospholipids; D014280:Triglycerides; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D011341:Probucol