{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:19:44Z","timestamp":1791285584312,"version":"4.1.0"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2001,11]]},"abstract":"<jats:p>\n            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\n            <jats:sub>6<\/jats:sub>\n            , B\n            <jats:sub>12<\/jats:sub>\n            , 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 behind homocysteine-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 by this 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 metalloproteinases-1 and \u03b11(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 in the development of hyperhomocysteinemia and (2) a role for elevated homocysteine levels in the development of liver fibrosis.\n          <\/jats:p>","DOI":"10.1161\/hy1101.099499","type":"journal-article","created":{"date-parts":[[2007,9,28]],"date-time":"2007-09-28T18:37:17Z","timestamp":1191004637000},"page":"1217-1221","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":98,"title":["Hyperhomocysteinemia in Liver Cirrhosis"],"prefix":"10.1161","volume":"38","author":[{"given":"Elena Ruiz","family":"Garci\u0301a-Tevijano","sequence":"first","affiliation":[{"name":"From the Divisio\u0301n de Hepatologi\u0301a y Terapia Ge\u0301nica, Departamento de Medicina Interna (E.R.G.-T., C.B., F.J.C., J.M.M., M.A.A.) and Departamento de Cardiologi\u0301a y Cirugi\u0301a Cardiovascular (J.A.R., R.A.), Facultad de Medicina, Universidad de Navarra, Pamplona, Spain; Servicio de Cirugi\u0301a, Hospital Pri\u0301ncipe de Asturias, Alcala\u0301 de Henares (A.M.-D.), Madrid, Spain; and Servicio de Hepatologi\u0301a, IDIABAPS, Hospital Cli\u0301nic (J.C.), Barcelona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Berasain","sequence":"additional","affiliation":[{"name":"From the Divisio\u0301n de Hepatologi\u0301a y Terapia Ge\u0301nica, Departamento de Medicina Interna (E.R.G.-T., C.B., F.J.C., J.M.M., M.A.A.) and Departamento de Cardiologi\u0301a y Cirugi\u0301a Cardiovascular (J.A.R., R.A.), Facultad de Medicina, Universidad de Navarra, Pamplona, Spain; Servicio de Cirugi\u0301a, Hospital Pri\u0301ncipe de Asturias, Alcala\u0301 de Henares (A.M.-D.), Madrid, Spain; and Servicio de Hepatologi\u0301a, IDIABAPS, Hospital Cli\u0301nic (J.C.), Barcelona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose\u0301 Antonio","family":"Rodri\u0301guez","sequence":"additional","affiliation":[{"name":"From the Divisio\u0301n de Hepatologi\u0301a y Terapia Ge\u0301nica, Departamento de Medicina Interna (E.R.G.-T., C.B., F.J.C., J.M.M., M.A.A.) and Departamento de Cardiologi\u0301a y Cirugi\u0301a Cardiovascular (J.A.R., R.A.), Facultad de Medicina, Universidad de Navarra, Pamplona, Spain; Servicio de Cirugi\u0301a, Hospital Pri\u0301ncipe de Asturias, Alcala\u0301 de Henares (A.M.-D.), Madrid, Spain; and Servicio de Hepatologi\u0301a, IDIABAPS, Hospital Cli\u0301nic (J.C.), Barcelona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando Jose\u0301","family":"Corrales","sequence":"additional","affiliation":[{"name":"From the Divisio\u0301n de Hepatologi\u0301a y Terapia Ge\u0301nica, Departamento de Medicina Interna (E.R.G.-T., C.B., F.J.C., J.M.M., M.A.A.) and Departamento de Cardiologi\u0301a y Cirugi\u0301a Cardiovascular (J.A.R., R.A.), Facultad de Medicina, Universidad de Navarra, Pamplona, Spain; Servicio de Cirugi\u0301a, Hospital Pri\u0301ncipe de Asturias, Alcala\u0301 de Henares (A.M.-D.), Madrid, Spain; and Servicio de Hepatologi\u0301a, IDIABAPS, Hospital Cli\u0301nic (J.C.), Barcelona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Arias","sequence":"additional","affiliation":[{"name":"From the Divisio\u0301n de Hepatologi\u0301a y Terapia Ge\u0301nica, Departamento de Medicina Interna (E.R.G.-T., C.B., F.J.C., J.M.M., M.A.A.) and Departamento de Cardiologi\u0301a y Cirugi\u0301a Cardiovascular (J.A.R., R.A.), Facultad de Medicina, Universidad de Navarra, Pamplona, Spain; Servicio de Cirugi\u0301a, Hospital Pri\u0301ncipe de Asturias, Alcala\u0301 de Henares (A.M.-D.), Madrid, Spain; and Servicio de Hepatologi\u0301a, IDIABAPS, Hospital Cli\u0301nic (J.C.), Barcelona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Marti\u0301n-Duce","sequence":"additional","affiliation":[{"name":"From the Divisio\u0301n de Hepatologi\u0301a y Terapia Ge\u0301nica, Departamento de Medicina Interna (E.R.G.-T., C.B., F.J.C., J.M.M., M.A.A.) and Departamento de Cardiologi\u0301a y Cirugi\u0301a Cardiovascular (J.A.R., R.A.), Facultad de Medicina, Universidad de Navarra, Pamplona, Spain; Servicio de Cirugi\u0301a, Hospital Pri\u0301ncipe de Asturias, Alcala\u0301 de Henares (A.M.-D.), Madrid, Spain; and Servicio de Hepatologi\u0301a, IDIABAPS, Hospital Cli\u0301nic (J.C.), Barcelona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Caballeri\u0301a","sequence":"additional","affiliation":[{"name":"From the Divisio\u0301n de Hepatologi\u0301a y Terapia Ge\u0301nica, Departamento de Medicina Interna (E.R.G.-T., C.B., F.J.C., J.M.M., M.A.A.) and Departamento de Cardiologi\u0301a y Cirugi\u0301a Cardiovascular (J.A.R., R.A.), Facultad de Medicina, Universidad de Navarra, Pamplona, Spain; Servicio de Cirugi\u0301a, Hospital Pri\u0301ncipe de Asturias, Alcala\u0301 de Henares (A.M.-D.), Madrid, Spain; and Servicio de Hepatologi\u0301a, IDIABAPS, Hospital Cli\u0301nic (J.C.), Barcelona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose\u0301 Mari\u0301a","family":"Mato","sequence":"additional","affiliation":[{"name":"From the Divisio\u0301n de Hepatologi\u0301a y Terapia Ge\u0301nica, Departamento de Medicina Interna (E.R.G.-T., C.B., F.J.C., J.M.M., M.A.A.) and Departamento de Cardiologi\u0301a y Cirugi\u0301a Cardiovascular (J.A.R., R.A.), Facultad de Medicina, Universidad de Navarra, Pamplona, Spain; Servicio de Cirugi\u0301a, Hospital Pri\u0301ncipe de Asturias, Alcala\u0301 de Henares (A.M.-D.), Madrid, Spain; and Servicio de Hepatologi\u0301a, IDIABAPS, Hospital Cli\u0301nic (J.C.), Barcelona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mati\u0301as Antonio","family":"Avila","sequence":"additional","affiliation":[{"name":"From the Divisio\u0301n de Hepatologi\u0301a y Terapia Ge\u0301nica, Departamento de Medicina Interna (E.R.G.-T., C.B., F.J.C., J.M.M., M.A.A.) and Departamento de Cardiologi\u0301a y Cirugi\u0301a Cardiovascular (J.A.R., R.A.), Facultad de Medicina, Universidad de Navarra, Pamplona, Spain; Servicio de Cirugi\u0301a, Hospital Pri\u0301ncipe de Asturias, Alcala\u0301 de Henares (A.M.-D.), Madrid, Spain; and Servicio de Hepatologi\u0301a, IDIABAPS, Hospital Cli\u0301nic (J.C.), Barcelona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0955-2863(90)90070-2"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.49.1.31"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(95)00508-0"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1993.03510220049033"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0163-7258(96)00197-0"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/63.2.220"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1530-0277.1993.tb00820.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1159\/000201425"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510230314"},{"key":"e_1_3_2_10_2","first-page":"1310","volume":"22","year":"1995","unstructured":"Varela-Moreiras G, Alonso-Aperte E, Rubio M, Gasso M, Deulofeu R, Alvarez L, Caballeria J, Rodes J, Mato JM. Carbon tetrachloride-induced hepatic injury is associated with global DNA hypomethylation and homocysteinemia: effect of S-adenosylmethionine treatment. 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