Effects of atorvastatin treatment on the oxidatively modified low density lipoprotein in hyperlipidemic patients.
Atorvastatin is an established HMG-CoA reductase inhibitor which effectively reduces the plasma low density lipoprotein (LDL)-cholesterol level in hyperlipidemic patients. The present study was designed to investigate whether atorvastatin treatment can modify the biochemical content of oxidized LDL in hyperlipidemic patients and the ability of oxidized LDL to impair the endothelium-dependent relaxation of blood vessels. With atorvastatin (10 mg/day) treatment for 4 weeks in 19 type IIa hyperlipidemic patients, total cholesterol level was lowered by 23%, LDL-cholesterol was lowered by 32% and triacylglycerol was lowered by 19% as compared with dietary therapy alone. High density lipoprotein levels increased by approximately 9%. The ability of oxidized LDL from hyperlipidemic patients after atorvastatin treatment to impair the endothelium-dependent relaxation was significantly reduced as compared with dietary intervention alone. Analysis of the biochemical contents of oxidized LDL from this group revealed that there was an 11% reduction in lysophosphatidylcholine (LPC) as compared with the group that received only dietary counseling. A decrease in the C16:0 moiety with a corresponding increase in the C18:0 moiety of LPC in the oxidized LDL was also observed in the atorvastatin treated group. We propose that the observed reduction and the change in composition of acyl groups in LPC in the oxidized LDL of the atorvastatin-treated group results from a combination of the continued dietary treatment as well as drug therapy. In view of an observation that both C16:0 and C18:0 LPC species are equally potent in the impairment of endothelium-dependent relaxation of the aortic rings, we feel that the reduced level of LPC in the oxidized LDL produced by atorvastatin treatment is partially responsible for the improvement in endothelium control of vascular tone.
Zhu
Q
Q
Lipid Research Group, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
McMaster
J
J
Mymin
D
D
Dembinski
T
T
Hatch
G
G
Choy
P C
PC
Kroeger
E A
EA
D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D003131:Combined Modality Therapy; D004035:Diet Therapy; D004730:Endothelium, Vascular / Q000187:drug effects; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy*; D008077:Lipoproteins, LDL / Q000097:blood*; D008244:Lysophosphatidylcholines / Q000097:blood; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000097:blood; D011758:Pyrroles / Q000627:therapeutic use*
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D010743:Phospholipids; D011758:Pyrroles; D000069059:Atorvastatin