Fluvastatin reverses endothelial dysfunction and increased vascular oxidative stress in rat adjuvant-induced arthritis
dc.contributor.author | Haruna, Yoshisuke | en_US |
dc.contributor.author | Morita, Yoshitaka | en_US |
dc.contributor.author | Yada, Toyotaka | en_US |
dc.contributor.author | Satoh, Minoru | en_US |
dc.contributor.author | Fox, David A. | en_US |
dc.contributor.author | Kashihara, Naoki | en_US |
dc.date.accessioned | 2007-09-20T18:37:27Z | |
dc.date.available | 2008-09-08T14:25:14Z | en_US |
dc.date.issued | 2007-06 | en_US |
dc.identifier.citation | Haruna, Yoshisuke; Morita, Yoshitaka; Yada, Toyotaka; Satoh, Minoru; Fox, David A.; Kashihara, Naoki (2007)."Fluvastatin reverses endothelial dysfunction and increased vascular oxidative stress in rat adjuvant-induced arthritis." Arthritis & Rheumatism 56(6): 1827-1835. <http://hdl.handle.net/2027.42/56040> | en_US |
dc.identifier.issn | 0004-3591 | en_US |
dc.identifier.issn | 1529-0131 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/56040 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=17530711&dopt=citation | en_US |
dc.description.abstract | Objective To investigate the effect of statins on vascular dysfunction in rat adjuvant-induced arthritis (AIA). Methods Fluvastatin (5 mg/kg/day) was administered orally to rats with AIA, for 21 days after the onset of arthritis. The vasodilatory response to acetylcholine of aortic rings isolated from rats with AIA that were not treated or were treated with fluvastatin and from normal rats was determined. The amounts of 4-hydroxy-2-nonenal (HNE) and nitrotyrosine in aortas were measured by Western blotting. In vitro and in situ superoxide production in aortas was evaluated based on fluorogenic oxidation of dihydroethidium to ethidium. Expression of NAD(P)H components and endothelial nitric oxide synthase (eNOS) in aortas was examined by real-time reverse transcriptase–polymerase chain reaction and Western blotting. Serum levels of tetrahydrobiopterin, a critical eNOS cofactor, were determined by high-performance liquid chromatography. Results Fluvastatin reversed endothelial dysfunction in AIA without affecting the clinical severity of arthritis or serum cholesterol concentration. Fluvastatin reduced the amounts of HNE and nitrotyrosine in the aorta, and the levels of superoxide expressed in endothelial cells and smooth muscle cells in the tissue, in rats with AIA. NADH- or L -arginine–induced superoxide production was not observed in the aortic samples from fluvastatin-treated rats with AIA. Fluvastatin decreased the levels of expression of messenger RNA for p22phox, a NAD(P)H oxidase component, in the aortas of rats with AIA, but did not affect the expression of eNOS. Serum levels of tetrahydrobiopterin were significantly reduced in rats with AIA, and were increased by administration of fluvastatin. Conclusion Our findings demonstrate that fluvastatin has potent vascular protective effects in AIA and provide additional scientific rationale for the use of statins to reduce cardiovascular mortality in patients with rheumatoid arthritis. | en_US |
dc.format.extent | 349077 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.title | Fluvastatin reverses endothelial dysfunction and increased vascular oxidative stress in rat adjuvant-induced arthritis | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Geriatrics | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | University of Michigan, Ann Arbor | en_US |
dc.contributor.affiliationother | Kawasaki Medical School, Kurashiki, Japan | en_US |
dc.contributor.affiliationother | Kawasaki Medical School, Kurashiki, Japan ; Division of Nephrology and Rheumatology, Department of Internal Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192, Japan | en_US |
dc.contributor.affiliationother | Kawasaki Medical School, Kurashiki, Japan | en_US |
dc.contributor.affiliationother | Kawasaki Medical School, Kurashiki, Japan | en_US |
dc.contributor.affiliationother | Kawasaki Medical School, Kurashiki, Japan | en_US |
dc.identifier.pmid | 17530711 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/56040/1/22632_ftp.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1002/art.22632 | en_US |
dc.identifier.source | Arthritis & Rheumatism | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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