Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Induction of oxidative stress by homocyst(e)ine impairs endothelial function
Autore:
Mujumdar, VS; Aru, GM; Tyagi, SC;
Indirizzi:
Univ Mississippi, Med Ctr, Sch Med, Dept Physiol & Biophys, Jackson, MS 39216 USA Univ Mississippi Jackson MS USA 39216 ol & Biophys, Jackson, MS 39216 USA Univ Mississippi, Med Ctr, Sch Med, Div Cardiothorac Surg, Jackson, MS 39216 USA Univ Mississippi Jackson MS USA 39216 othorac Surg, Jackson, MS 39216 USA
Titolo Testata:
JOURNAL OF CELLULAR BIOCHEMISTRY
fascicolo: 3, volume: 82, anno: 2001,
pagine: 491 - 500
SICI:
0730-2312(2001)82:3<491:IOOSBH>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
SMOOTH-MUSCLE CELLS; NITRIC-OXIDE; MATRIX METALLOPROTEINASES; INDUCED ARTERIOSCLEROSIS; VASCULAR TONE; HOMOCYSTEINE; EXPRESSION; RAT; PEROXYNITRITE; DYSFUNCTION;
Keywords:
vascular compliance; ECM remodeling; hypertrophy; aorta; hypertension; elastin; collagen; smooth muscle; fibrosis; organ culture; caspase; vasospasm; apoptosis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
46
Recensione:
Indirizzi per estratti:
Indirizzo: Tyagi, SC Univ Mississippi, Med Ctr, Sch Med, Dept Physiol & Biophys, 2500N State St, Jackson, MS 39216 USA Univ Mississippi 2500 N State St JacksonMS USA 39216 39216 USA
Citazione:
V.S. Mujumdar et al., "Induction of oxidative stress by homocyst(e)ine impairs endothelial function", J CELL BIOC, 82(3), 2001, pp. 491-500

Abstract

Previous studies have demonstrated a relationship between hyperhomocysteinemia and endothelial dysfunction, reduced bioavailability of nitric oxide, elastinolysis, and vascular muscle cell proliferation. In vivo decreased nitric oxide production is associated with increased matrix metalloproteinase(MMP) activity and formation of nitrotyrosine. To test the hypothesis thathomocysteine neutralizes vascular endothelial nitric oxide, activates metalloproteinase, causes elastinolysis and vascular hypertrophy, we isolated aortas from normotensive Wistar rats and cultured them in medium containing homocysteine, and calf serum for 14 days. Homocysteine-mediated impairment of endothelial-dependent vasodilatation was reversed by co-incubation of homocysteine with nicotinamide (an inhibitor of peroxinitrite and nitrotyrosine), suggesting a role of homocysteine in redox-mediating endothelial dysfunction and nitrotyrosine formation. The Western blot analysis, using anti-nitrotyrosine antibody, on aortic tissue homogeneates demonstrated decreasednitrotyrosine in hyperhomocysteinemic vessels treated with nicotinamide. Zymographic analysis revealed increased elastinolytic gelatinase A and B (MMP-2,-9) in homocysteine treated vessels and the treatment with nicotinamidedecreases the homocysteine-induced MMP activation. Morphometric analyses revealed significant medial hypertrophic thickening (1.4 +/-0.2-fold of control, P = 0.03) and elastin disruption in homocysteine-treated vessels as compared to control. To determine whether homocysteine causes endothelial cell injury, cross-sections of aortas were analyzed for caspase activity by incubating with Ac-YVAD-AMC (substrate for apoptotic enzyme, caspase). The endothelium of homocysteine treated vessels, and endothelial cells treated with homocysteine, showed marked labeling for caspase. The length-tension relationship of homocysteine treated aortas was shifted to the left as compared to untreated aortas, indicating reduced vascular elastic compliance in homocysteine-treated vessels. Coincubation of homocysteine and inhibitors of MMP, tissue inhibitor of metalloproteinase-4 (TIMP-4), and caspase, YVAD-CHO, improved vascular function. The results suggest that alteration in vascular elastin/collagen ratio and activation of MMP-2 are associated with decreased NO production in hyperhomocysteinemia. (C) 2001 Wiley-Liss, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/04/20 alle ore 20:05:16