title: Rosuvastatin attenuates monocyte-endothelial cell interactions and vascular free radical production in hypercholesterolemic mice.
abstract: One of the earliest observable events in atherogenesis is enhanced monocyte adhesion to the endothelium. In addition to reducing circulating levels of cholesterol, 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) are thought to have direct salutary effects upon vascular cells. We hypothesized that the new statin, rosuvastatin, would have anti-inflammatory effects on the vessel wall. Eight-week-old apolipoprotein E-deficient mice were fed a normal chow diet for a period of 12 weeks. During this time mice were administered vehicle or rosuvastatin at a dose of 0, 1, 5, or 20 mg/kg by subcutaneous injection at the same time daily for a period of 2 or 6 weeks prior to sacrifice. At the end of the study, rosuvastatin-treated animals displayed lower plasma total cholesterol levels, whereas showing little change in high-density lipoprotein cholesterol or triglycerides. Using a functional binding assay, we also demonstrated that endothelial adhesiveness for monocytes was significantly attenuated after 2 weeks of treatment with rosuvastatin. Quantitative real-time polymerase chain reaction determined that rosuvastatin reduced the expression of vascular cell adhesion molecule-1, monocyte chemotactic protein-1, and metalloproteinase-9 in the vessel wall. In addition, rosuvastatin inhibited vascular expression of p22(phox) and superoxide production, as well as diminishing plasma 8-isoprostanes concentrations. Thus, treatment with rosuvastatin has acute anti-inflammatory actions that likely participate in its beneficial actions during atherogenesis.
authors.affiliation: Division of Cardiovascular Medicine, Stanford University School of Medicine, CA 94305-5246, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Tomoko
authors.initials: T
authors.lastname: Asagami
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Matsushita
authors.forename: Keun-Ho
authors.initials: KH
authors.lastname: Lee
authors.forename: Philip S
authors.initials: PS
authors.lastname: Tsao
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002450:Cell Communication / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005260:Female; D005464:Fluorobenzenes / Q000494:pharmacology* / Q000627:therapeutic use; D005609:Free Radicals / Q000378:metabolism; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D005464:Fluorobenzenes; D005609:Free Radicals; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium