title: Atorvastatin induces associated reductions in platelet P-selectin, oxidized low-density lipoprotein, and interleukin-6 in patients with coronary artery diseases.
abstract: The development and progression of atherosclerosis comprises various processes, such as endothelial dysfunction, chronic inflammation, thrombus formation, and lipid profile modification. Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that have pleiotropic effects in addition to cholesterol-lowering properties. However, the mechanisms of these effects are not completely understood. Here, we investigated whether atorvastatin affects the levels of malondialdehyde-modified low-density lipoprotein (MDALDL), an oxidized LDL, the proinflammatory cytokine interleukin-6 (IL-6), or platelet P-selectin, a marker of platelet activation, relative to that of LDL cholesterol (LDL-C). Forty-eight patients with coronary artery disease and hyperlipidemia were separated into two groups that were administered with (atorvastatin group) or without (control group) atorvastatin. The baseline MDA-LDL level in all participants significantly correlated with LDL-C (r = 0.71, P < 0.01) and apolipoprotein B levels (r = 0.66, P < 0.01). Atorvastatin (10 mg/day) significantly reduced the LDL-C level within 4 weeks and persisted for a further 8 weeks of administration. Atorvastatin also reduced the MDA-LDL level within 4 weeks and further reduced it over the next 8 weeks. Platelet P-selectin expression did not change until 4 weeks of administration and then significantly decreased at 12 weeks, whereas the IL-6 level was gradually, but not significantly, reduced at 12 weeks. In contrast, none of these parameters significantly changed in the control group within these time frames. The reduction (%) in IL-6 between 4 and 12 weeks after atorvastatin administration significantly correlated with that of MDALDL and of platelet P-selectin (r = 0.65, P < 0.05 and r = 0.70, P < 0.05, respectively). These results suggested that the positive effects of atorvastatin on the LDL-C oxidation, platelet activation and inflammation that are involved in atherosclerotic processes are exerted in concert after lowering LDL-C.
authors.affiliation: Second Department of Internal Medicine, School of Medicine, Nagasaki University, Nagasaki, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Oka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ikeda
authors.forename: Seiji
authors.initials: S
authors.lastname: Koga
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Miyahara
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D000368:Aged; D000069059:Atorvastatin; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003131:Combined Modality Therapy; D003324:Coronary Artery Disease / Q000097:blood / Q000178:diet therapy / Q000188:drug therapy*; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000178:diet therapy / Q000188:drug therapy*; D015850:Interleukin-6 / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood*; D011758:Pyrroles / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015850:Interleukin-6; D008077:Lipoproteins, LDL; D019007:P-Selectin; D011758:Pyrroles; D014280:Triglycerides; C099252:oxidized low density lipoprotein; D008315:Malondialdehyde; D002784:Cholesterol; D000069059:Atorvastatin