Ezetimibe decreases serum amyloid A levels in HDL3 in hemodialysis patients.
OBJECTIVE
The aim of this study was to investigate the effects of ezetimibe on high-density lipoprotein (HDL) subspecies and serum amyloid A (SAA), an apolipoprotein mainly bound and transported by HDL particles, in patients with end-stage renal disease (ERSD), a condition typically characterized by high SAA- and low HDL-cholesterol (C ) levels.


METHODS
26 ERSD patients receiving hemodialysis (HD) were given ezetimibe (10 mg/d) for 6 - 8 weeks. HDL3 was separated from serum by a single precipitation method established by our group. HDL2 was estimated by subtracting HDL3 from total HDL. Serum amyloid A (SAA) was measured by the ELISA method.


RESULTS
Ezetimibe significantly reduced remnant-like particle (RLP)-C, low-density lipoprotein (LDL)-C, and apolipoprotein (apo) B without affecting triglyceride, HDL-C and LCAT activities. HDL2-C levels were lower and HDL3-C was substantially lower in the HD patients than in the controls. Ezetimibe increased HDL2-apoAI but decreased HDL3-apoAI without affecting serum apoAI or AII. HDL-SAA was 5-fold higher in the HD patients than in the controls (56 ± 49 vs. 12 ± 9 µg/ml). Ezetimibe decreased HDL-SAA by 43 % (to 32 ± 36 µg/ml), and this inhibitory effect was exclusively attributable to a 72% reduction in HDL3-SAA in response to the ezetimibe treatment. The reduction of HDL3-SAA was significantly associated with increased HDL2-apo AI and reduced HDL3-apo AI.


CONCLUSIONS
Ezetimibe treatment decreased "inflammatory" (SAA-containing) HDL3, and may thus have restored the anti-atherogenic function of HDL particles in ESRD patients.
Hirano
T
T
Department of Diabetes, Metabolism and Endocrinology, Showa University School of Medicine, Tokyo, Japan. hirano@med.showa-u.ac.jp
Nohtomi
K
K
Nakanishi
N
N
Watanabe
T
T
Hyodo
T
T
Taira
T
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D016632:Apolipoprotein A-I / Q000097:blood; D001384:Azetidines / Q000494:pharmacology*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D053440:Lipoproteins, HDL3 / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D000685:Serum Amyloid A Protein / Q000032:analysis*
D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; D001384:Azetidines; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D053440:Lipoproteins, HDL3; D000685:Serum Amyloid A Protein; D000069438:Ezetimibe