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Titolo:
Hyperhomocysteinemia in liver cirrhosis mechanisms and role in vascular and hepatic fibrosis
Autore:
Garcia-Tevijano, ER; Berasain, C; Rodriguez, JA; Corrales, FJ; Arias, R; Martin-Duce, A; Caballeria, J; Mato, JM; Avila, MA;
Indirizzi:
Univ Navarra, Fac Med, Dept Med Interna, Div Hepatol & Terapia Gen, Pamplona 31008, Spain Univ Navarra Pamplona Spain 31008 l & Terapia Gen, Pamplona 31008, Spain Univ Navarra, Fac Med, Dept Cardiol & Cirugia Cardiovasc, Pamplona 31008, Spain Univ Navarra Pamplona Spain 31008 ugia Cardiovasc, Pamplona 31008, Spain Hosp Principe Asturias, Serv Cirugia, Madrid, Spain Hosp Principe Asturias Madrid Spain turias, Serv Cirugia, Madrid, Spain Hosp Clin Barcelona, IDIABAPS, Serv Hepatol, Barcelona, Spain Hosp Clin Barcelona Barcelona Spain APS, Serv Hepatol, Barcelona, Spain
Titolo Testata:
HYPERTENSION
fascicolo: 5, volume: 38, anno: 2001,
pagine: 1217 - 1221
SICI:
0194-911X(200111)38:5<1217:HILCMA>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
METHIONINE METABOLISM; PLASMA HOMOCYSTEINE; DNA HYPOMETHYLATION; DISEASE; ATHEROSCLEROSIS; INCREASES; GROWTH; MATRIX; CELLS;
Keywords:
homocysteine; methionine; muscle, smooth, vascular; liver; cirrhosis; fibrosis; gene expression;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
27
Recensione:
Indirizzi per estratti:
Indirizzo: Avila, MA Univ Navarra, Fac Med, Dept Med Interna, Div Hepatol & Terapia Gen, Edificio Los Castanos,C Irunlarrea 1, Pamplona 31008, Spain Univ Navarra Edificio Los Castanos,C Irunlarrea 1 Pamplona Spain 31008
Citazione:
E.R. Garcia-Tevijano et al., "Hyperhomocysteinemia in liver cirrhosis mechanisms and role in vascular and hepatic fibrosis", HYPERTENSIO, 38(5), 2001, pp. 1217-1221

Abstract

Numerous clinical and epidemiological studies have identified elevated homocysteine levels in plasma as a risk factor for atherosclerotic vascular disease and thromboembolism. Hyperhomocysteinemia may develop as a consequence of defects in homocysteine-metabolizing genes; nutritional conditions leading to vitamin B-6, B-12, or folate deficiencies; or chronic alcohol consumption. Homocysteine is an intermediate in methionine metabolism, which takes place mainly in the liver. Impaired liver function leads to altered methionine and homocysteine metabolism; however, the molecular basis for such alterations is not completely understood. In addition, the mechanisms behindhomocysteine-induced cellular toxicity are not fully defined. In the present work, we have examined the expression of the main enzymes involved in methionine and homocysteine metabolism, along with the plasma levels of methionine and homocysteine, in the liver of 26 cirrhotic patients and 10 control subjects. To gain more insight into the cellular effects of elevated homocysteine levels, we have searched for changes in gene expression induced bythis amino acid in cultured human vascular smooth muscle cells. We have observed a marked reduction in the expression of the main genes involved in homocysteine metabolism in liver cirrhosis. In addition, we have identified the tissue inhibitor of metalloprotemases-1 and alpha1(I)procollagen to be upregulated in vascular smooth muscle cells and liver stellate cells exposed to pathological concentrations of homocysteine. Taken together, our observations suggest (1) impaired liver function could be a novel determinant inthe development of hyperhomocysteinemia and (2) a role for elevated homocysteine levels in the development of liver Fibrosis.

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Documento generato il 27/11/20 alle ore 00:37:57