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Titolo:
In vivo anti-inflammatory effect of statins is mediated by nonsterol mevalonate products
Autore:
Diomede, L; Albani, D; Sottocorno, M; Donati, MB; Bianchi, M; Fruscella, P; Salmona, M;
Indirizzi:
Ist Ric Farmacol Mario Negri, Dept Mol Biochem & Pharmacol, I-20157 Milan,Italy Ist Ric Farmacol Mario Negri Milan Italy I-20157 ol, I-20157 Milan,Italy Consorzio Mario Negri Sud, Dept Med & Vasc Pharmacol, Chieti, Italy Consorzio Mario Negri Sud Chieti Italy & Vasc Pharmacol, Chieti, Italy
Titolo Testata:
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
fascicolo: 8, volume: 21, anno: 2001,
pagine: 1327 - 1332
SICI:
1079-5642(200108)21:8<1327:IVAEOS>2.0.ZU;2-X
Fonte:
ISI
Lingua:
ENG
Soggetto:
MONOCYTE CHEMOATTRACTANT PROTEIN-1; AVERAGE CHOLESTEROL LEVELS; SQUALENE SYNTHASE; LEUKOCYTE RECRUITMENT; CORONARY EVENTS; INHIBITION; REDUCTASE; ATHEROSCLEROSIS; CHEMOKINES; LOVASTATIN;
Keywords:
statins; HMG-CoA reductase; squalene synthetase; interleukin-6; chemokines;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Diomede, L Ist Ric Farmacol Mario Negri, Dept Mol Biochem & Pharmacol, ViaEritrea 62, I-20157 Milan, Italy Ist Ric Farmacol Mario Negri Via Eritrea 62 Milan Italy I-20157
Citazione:
L. Diomede et al., "In vivo anti-inflammatory effect of statins is mediated by nonsterol mevalonate products", ART THROM V, 21(8), 2001, pp. 1327-1332

Abstract

This study set out to clarify whether the inhibition of sterol or nonsterol derivatives arising from mevalonate biotransformation plays a major role in the in vivo anti-inflammatory action of statins. Hepatic synthesis of all these derivatives was inhibited in mice by administered statins, whereas squalestatin inhibited only sterol derivatives. Using a short-term treatment schedule, we found that statins reduced the hepatic activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase without affecting blood cholesterol. This treatment inhibited lipopolysaccharide- and carrageenan-induced pouchleukocyte recruitment and the exudate production of interleukin-6, monocyte chemotactic protein-1, and RANTES. Coadministration of mevalonate reversed the effect of statin on leukocyte recruitment. The inhibition of sterol synthesis by squalestatin did not have any anti-inflammatory effect, indicating that the biosynthesis of nonsterol compounds arising from mevalonate iscrucial for the in vivo regulation of cytokine and chemokine production bystatins. Their inhibition by statins may account for the reported anti-inflammatory effects of these drugs and may provide a biochemical basis for the recently reported effects of statins in the prevention of cardiovascular disease and mortality.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/04/20 alle ore 14:44:29