title: A HMG-CoA reductase inhibitor improved regression of atherosclerosis in the rabbit aorta without affecting serum lipid levels: possible relevance of up-regulation of endothelial NO synthase mRNA.
abstract: We determined the role of Fluvastatin: HMG-CoA reductase inhibitor on the regression of atherosclerosis following removal of dietary cholesterol. Male rabbits fed a 0.5% cholesterol diet for 12 weeks were divided into three groups: A1, hypercholesterolemic; A2, fed a regular diet for an 12 additional weeks; and A3, fed a regular diet with fluvastatin (2 mg/kg/day). Fluvastatin treatment (A3) did not affect serum lipid levels compared with A2. However, it decreased the atherosclerotic area in the aortic arch and decreased total and esterified cholesterol concentrations in the descending aorta. Tone-related basal NO release in the thoracic aorta was larger in A3 than in A2. eNOS mRNA in vessel was determined by competitive RT-PCR assay. It increased in A1, compared with normal aorta and decreased in A2; however, it did not decrease in A3. This is the first report of a decrease in eNOS mRNA in atherosclerosis after removal of dietary cholesterol and a reversal of it by a HMG-CoA reductase inhibitor, which may contribute to the regression of atherosclerosis.
authors.affiliation: Department of Geriatrics, Nagoya University Graduate School of Medicine, 466-8550, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kano
authors.forename: T
authors.initials: T
authors.lastname: Hayashi
authors.forename: D
authors.initials: D
authors.lastname: Sumi
authors.forename: T
authors.initials: T
authors.lastname: Esaki
authors.forename: Y
authors.initials: Y
authors.lastname: Asai
authors.forename: N K
authors.initials: NK
authors.lastname: Thakur
authors.forename: M
authors.initials: M
authors.lastname: Jayachandran
authors.forename: A
authors.initials: A
authors.lastname: Iguchi
mesh_terms: D000214:Acyl Coenzyme A / Q000037:antagonists & inhibitors*; D000818:Animals; D001011:Aorta / Q000201:enzymology* / Q000473:pathology; D001161:Arteriosclerosis / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D001835:Body Weight; D002791:Cholesterol, Dietary; D004730:Endothelium, Vascular / Q000201:enzymology / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D000077340:Fluvastatin; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006937:Hypercholesterolemia / Q000139:chemically induced / Q000188:drug therapy; D007211:Indoles / Q000627:therapeutic use*; D008055:Lipids / Q000097:blood*; D008297:Male; D009566:Nitrates / Q000097:blood; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D009573:Nitrites / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D013482:Superoxide Dismutase / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000214:Acyl Coenzyme A; D002791:Cholesterol, Dietary; D004791:Enzyme Inhibitors; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D008055:Lipids; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; C008047:3-hydroxy-3-methylglutaryl-coenzyme A; D000077340:Fluvastatin; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase