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Titolo:
Simvastatin preserves coronary endothelial function in hypercholesterolemia in the absence of lipid lowering
Autore:
Wilson, SH; Simari, RD; Best, PJM; Peterson, TE; Lerman, LO; Aviram, M; Nath, KA; Holmes, DR; Lerman, A;
Indirizzi:
Mayo Clin & Mayo Fdn, Div Cardiovasc Dis & Internal Med, Rochester, MN 55905 USA Mayo Clin & Mayo Fdn Rochester MN USA 55905 Med, Rochester, MN 55905 USA Mayo Clin & Mayo Fdn, Div Hypertens, Rochester, MN 55905 USA Mayo Clin & Mayo Fdn Rochester MN USA 55905 tens, Rochester, MN 55905 USA Technion Israel Inst Technol, Rappaport Family Inst Res Med Sci, Lipid ResLab, IL-31096 Haifa, Israel Technion Israel Inst Technol Haifa Israel IL-31096 L-31096 Haifa, Israel
Titolo Testata:
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
fascicolo: 1, volume: 21, anno: 2001,
pagine: 122 - 128
SICI:
1079-5642(200101)21:1<122:SPCEFI>2.0.ZU;2-3
Fonte:
ISI
Lingua:
ENG
Soggetto:
NITRIC-OXIDE SYNTHASE; REDUCTASE INHIBITORS; DEPENDENT RELAXATION; CELL-ADHESION; L-ARGININE; CHOLESTEROL; ARTERY; VASOCONSTRICTION; PRAVASTATIN; THERAPY;
Keywords:
hypercholesterolemia; nitric oxide; vasorelaxation; endothelial NO synthase;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
39
Recensione:
Indirizzi per estratti:
Indirizzo: Lerman, A Mayo Clin, Div Cardiovasc Dis, 200 1st St SW, Rochester, MN 55905 USA Mayo Clin 200 1st St SW Rochester MN USA 55905 ter, MN 55905 USA
Citazione:
S.H. Wilson et al., "Simvastatin preserves coronary endothelial function in hypercholesterolemia in the absence of lipid lowering", ART THROM V, 21(1), 2001, pp. 122-128

Abstract

Recent evidence suggests that some benefit from the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors may occur independent of lipid lowering. We aimed to determine the effect Of simvastatin on coronary endothelial function, endothelial NO synthase (eNOS) expression, and oxidative stress in experimental hypercholesterolemia (HC) in the absence of cholesterol lowering. Pigs were randomized to 3 experimental groups: normal diet (N group),high cholesterol diet (HC group), and HC diet with simvastatin (HC+S group) for 12 weeks. Low density lipoprotein cholesterol was similarly increasedin the HC and HCS-S groups compared with the N group. In vitro analysis ofcoronary large- and small-vessel endothelium-dependent vasorelaxation was performed. The mean vasorelaxation of epicardial vessels to bradykinin was significantly attenuated in the HC group compared with the N group (32.3+/-1.2% versus 42.9+/-1.6%, respectively; P<0.0001), This attenuation was significantly reversed in the HC+S group (38.7+/-1.5%, P<0.005 versus HC group). The maximal vasorelaxation to substance P was significantly attenuated inthe HC group compared with the N group (50.5+/-11.9% versus 79.3+/-5.3%, respectively; P<0.05). This attenuated response was normalized in the HC+S group (74.9+/-4.1%, P<0.05 versus PIC group). The maximal arteriolar vasorelaxation to bradykinin was also significantly attenuated in the HC group compared with the N group (71.9+/-4.9% versus 96.8+/-1.34%, respectively; P<0.005), This was reversed in the HC+S group (98.4+/-0.6%, P<0.0001 versus HC group). Western blotting of coronary tissue homogenates for eNOS demonstrated a decrease in protein levels in the HC group compared with the N group, with normalization in the HC+S group. Elevation of plasma F-2-isoprostanes and thiobarbituric acid-reactive substances, markers of oxidative stress, occurred in the PIC compared with the N group. These changes were reversed in the HC+S group. Tn summary, simvastatin preserves endothelial function incoronary epicardial vessels and arterioles in experimental HC tin the absence of cholesterol lowering) in association with an increase in coronary eNOS levels and a decrease in oxidative stress, These alterations may play a role in the reduction in cardiac events after treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 23:55:04