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Titolo:
Simvastatin has anti-inflammatory and antiatherosclerotic activities independent of plasma cholesterol lowering
Autore:
Sparrow, CP; Burton, CA; Hernandez, M; Mundt, S; Hassing, H; Patel, S; Rosa, R; Hermanowski-Vosatka, A; Wang, PR; Zhang, DH; Peterson, L; Detmers, PA; Chao, YS; Wright, SD;
Indirizzi:
Merck Res Labs, Rahway, NJ 07065 USA Merck Res Labs Rahway NJ USA 07065Merck Res Labs, Rahway, NJ 07065 USA
Titolo Testata:
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
fascicolo: 1, volume: 21, anno: 2001,
pagine: 115 - 121
SICI:
1079-5642(200101)21:1<115:SHAAAA>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
APOE-DEFICIENT MICE; NITRIC-OXIDE SYNTHASE; HERITABLE HYPERLIPIDEMIC RABBITS; COA REDUCTASE INHIBITORS; LOW-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN-E; MESSENGER-RNA; UP-REGULATION; ATHEROSCLEROSIS; HYPERCHOLESTEROLEMIA;
Keywords:
atherosclerosis; apoE; mice; HMG-CoA reductase; inflammation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
47
Recensione:
Indirizzi per estratti:
Indirizzo: Sparrow, CP Merck Res Labs, Bldg 80 W,126 E Lincoln Ave, Rahway, NJ 07065 USA Merck Res Labs Bldg 80 W,126 E Lincoln Ave Rahway NJ USA 07065
Citazione:
C.P. Sparrow et al., "Simvastatin has anti-inflammatory and antiatherosclerotic activities independent of plasma cholesterol lowering", ART THROM V, 21(1), 2001, pp. 115-121

Abstract

Inhibitors of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase, such assimvastatin, lower circulating cholesterol levels and prevent myocardial infarction, Several studies have shown an unexpected effect of HMG-CoA reductase inhibitors on inflammation. Here, we confirm that simvastatin is anti-inflammatory by using a classic model of inflammation: carrageenan-induced foot pad edema. Simvastatin administered orally to mice 1 hour before carrageenan injection significantly reduced the extent of edema. Simvastatin wascomparable to indomethacin in this model. To determine whether the anti-inflammatory activity of simvastatin might affect atherogenesis, simvastatin was tested in mice deficient in apoE. Mice were dosed daily for 6 weeks with simvastatin (100 mg/kg body wt). Simvastatin did not alter plasma lipids. Atherosclerosis was quantified through the measurement of aortic cholesterol content. Aortas from control mice (n=20) contained 56+/-4 nmol total cholesterol/mg wet wt tissue, 38+/-2 nmol free cholesterol/mg, and 17+/-2 nmolcholesteryl ester/mg. Simvastatin (n=22) significantly (P<0.02) decreased these 3 parameters by 23%, 19%, and 34%, respectively. Histology of the atherosclerotic lesions showed that simvastatin did not dramatically alter lesion morphology, These data support the hypothesis that simvastatin has antiatherosclerotic activity beyond its plasma cholesterol-lowering activity.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 01:20:27