title: Atorvastatin markedly improves type III hyperlipoproteinemia in association with reduction of both exogenous and endogenous apolipoprotein B-containing lipoproteins.
abstract: Remnant lipoproteins are known to promote atherosclerosis especially in patients with type III hyperlipoproteinemia (HLP). In the current study, the effects of atorvastatin were investigated with special reference to the exogenous and endogenous apolipoprotein (apo) B-containing lipoprotein metabolism in type III HLP. Four Japanese male patients with type III HLP associated with homozygous apoE2 were studied. One-month administration of atorvastatin (20 mg once daily), after a 4-week dietary run-in, strikingly reduced serum total cholesterol and triglyceride (TG) levels by 52 (P<0.01) and 56% (P<0.05), respectively. Atorvastatin further decreased remnant-like particle (RLP)-cholesterol by 73% and RLP-TG by 65% (P<0.05), respectively. Distribution analysis by polyacrylamide gel disc electrophoresis clearly showed that atorvastatin diminished very low-, intermediate- and low-density lipoprotein particles. The relative particle diameter of intermediate-density lipoprotein became smaller after atorvastatin treatment (P<0.01). Furthermore, ultracentrifugal analysis demonstrated that atorvastatin significantly decreased cholesterol, TG and phospholipid concentrations in all apoB-containing lipoprotein fractions and very low-density lipoprotein (VLDL)-cholesterol/serum TG ratio (P<0.05), implying atorvastatin-induced reduction of beta-VLDL. Finally, newly developed assays of apoB-48 and apoB-100 revealed that atorvastatin markedly reduced these apolipoproteins by 43 and 52%, respectively (P<0.01), suggesting that atorvastatin decreased the number of both exogenous and endogenous apoB-containing lipoproteins. Taken together, atorvastatin improves remnant lipoprotein metabolism in type III HLP both in quality and in quantity. Atorvastatin can be one of the optimal options for the treatment of patients with type III HLP.
authors.affiliation: Department of Internal Medicine and Molecular Science, Graduate School of Medicine, B5, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Ishigami
authors.forename: Shizuya
authors.initials: S
authors.lastname: Yamashita
authors.forename: Naohiko
authors.initials: N
authors.lastname: Sakai
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Hirano
authors.forename: Hisatoyo
authors.initials: H
authors.lastname: Hiraoka
authors.forename: Tadashi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuzawa
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001053:Apolipoproteins / Q000097:blood; D001055:Apolipoproteins B / Q000097:blood*; D000069059:Atorvastatin; D002784:Cholesterol / Q000097:blood; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D006952:Hyperlipoproteinemia Type III / Q000097:blood* / Q000188:drug therapy*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood* / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D011758:Pyrroles / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
chemical_list: D000924:Anticholesteremic Agents; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001053:Apolipoproteins; D001055:Apolipoproteins B; D006538:Heptanoic Acids; D008055:Lipids; D008074:Lipoproteins; D011758:Pyrroles; D014280:Triglycerides; D002784:Cholesterol; D000069059:Atorvastatin