Metabolic interactions between hyperhomocysteinemia and endothelin-1 among Tunisian patients with acute coronary diseases

BACKGROUND: Acute coronary syndromes (ACS) are complex and polygenic diseases which are a real problem of public health. These syndromes require multidisciplinary studies to understand the pathogenesis mechanisms and metabolic interactions between different risk factors.This study aimed to explore the variation of two coronary risk parameters not mentioned by Framingham cohorts, hyperhomocysteinemia and endothelin-1 (ET-1) in Tunisian coronary and the study of the variation of these parameters based on various cardiac risk factors and metabolic relationship between them.To 157 coronary and 142 healthy subjects, the concentration of homocysteine was quantified by fluorescence polarization immunoassay; the concentration of ET-1 was measured by an analytical technique, the High Performance Liquid Chromatography (HPLC) coupled with mass spectrometry. RESULTS: Our study showed that homocysteine and ET-1 were significantly higher in patients compared to healthy subjects (24.40 ± 12.5 µmol/L vs 7.44 ± 2.5 µmol/L p <0.00001) for homocysteine and (15.2 ± 5.3 nmol/L vs 7.1 ± 2.7 nmol/L, p <0.00001) for ET-1. On the other hand, homocysteine varies according to tobacco and diabetes while ET-1 depends on the sex, hypertension, smoking, obesity and dyslipidemia and a statistically negative correlation was shown between homocysteine and ET-1 in coronary patients (r = -0.66 p <0.00001. CONCLUSION: The study of the variation of these two parameters in coronary patients and metabolic exploration of the relationship between homocysteine and ET-1 according to various risk factors and the interactions between themselves facilitates the decision of therapeutic treatment.

Changes in Body Composition Predict Homocysteine Changes and Hyperhomocysteinemia in Korea

Cardiovascular disease (CVD) is the primary cause of death in Korea. Hyperhomocysteinemia confers an independent risk for CVD comparable to the risk of smoking and hyperlipidemia. The purpose of this study was to assess the effect of cardiovascular risk factors and body composition change on homocysteine (Hcy) levels in Korean men and women. The association between body composition and Hcy levels was investigated in a 2-yr prospective cohort study of 2,590 Koreans (mean age 45.5+/-9.6 yr). There were 293 cases of hyperhomocysteinemia (>14 microM/L) at follow-up. Increases in total body fat proportion and decreases in lean body mass (LBM) were significantly associated with increases in Hcy concentration after controlling for confounding factors. Further adjustments for behavioral factors showed that decreases in LBM were associated with Hcy increase. Decrease in LBM also predicted hyperhomocysteinemia at follow-up, after controlling for confounding factors. There was no significant association between change in body mass index (BMI) and Hcy concentrations over time. Hcy changes over time were related to change in LBM and body fat content, whereas BMI or weight change did not predict change in Hcy levels. Changes in ratio of LBM to total fat mass may contribute to hyperhomocysteinemia.

Biochemistry of homocysteine in health and diseases.

The amino acid homocysteine (Hcy), formed from methionine has profound importance in health and diseases. In normal circumstances, it is converted to cysteine and partly remethylated to methionine with the help of vit B12 and folate. However, when normal metabolism is disturbed, due to deficiency of cystathionine-beta-synthase, which requires vit B6 for activation, Hcy is accumulated in the blood with an increase of methionine, resulting into mental retardation (homocystinuria type I). A decrease of cysteine may cause eye diseases, due to decrease in the synthesis of glutathione (antioxidant). In homocystinurias type II, III and IV, there is accumulation of Hcy, but a decrease of methionine, thus, there is no mental retardation. Homocysteinemia is found in Marfan syndrome, some cases of type I diabetes and is also linked to smoking and has genetic basis too. In hyperhomocysteinemias (HHcys), clinical manifestations are mental retardation and seizures (type I only), ectopia lentis, secondary glaucoma, optic atrophy, retinal detachment, skeletal abnormalities, osteoporosis, vascular changes, neurological dysfunction and psychiatric symptoms. Thrombotic and cardiovascular diseases may also be encountered. The harmful effects of homocysteinemias are due to (i) production of oxidants (reactive oxygen species) generated during oxidation of Hcy to homocystine and disulphides in the blood. These could oxidize membrane lipids and proteins. (ii) Hcy can react with proteins with their thiols and form disulphides (thiolation), (iii) it can also be converted to highly reactive thiolactone which could react with the proteins forming -NH-CO- adducts, thus affecting the body proteins and enzymes. Homocystinuria type I is very rare (1 in 12 lakhs only) and is treated with supplementation of vit B6 and cystine. Others are more common and are treated with folate, vit B12 and in selected cases as in methionine synthase deficiency, methionine, avoiding excess. In this review, the role of elevated Hcy levels in cardiovascular, ocular, neurologial and other diseases and the possible therapeutic measures, in addition to the molecular mechanisms involved in deleterious manifestations of homocysteinemia, have been discussed.

Homocisteína e transtornos psiquiátricos / Homocysteine and neuropsychiatric disorders

O autor apresenta uma visão geral da literatura atual sobre homocisteína como um fator de risco para os transtornos neuropsiquiátricos. Foram pesquisados os bancos de dados MEDLINE, Current Contents e EMBASE (entre 1966 e 2002) para publicações em língua inglesa utilizando as palavras-chave Homocisteína e AVC; Doença de Alzheimer; Déficit Cognitivo, Epilepsia, Depressão ou Doença de Parkinson. Artigos individuais foram pesquisados para referências cruzadas relevantes. É biologicamente plausível que altos níveis de homocisteína possam causar lesão cerebral e transtornos neuropsiquiátricos. A homocisteína é pró-aterogênica e pró-trombótica. Dessa forma, aumenta o risco de acidente vascular cerebral, podendo ter um efeito neurotóxico direto. Evidências de que a homocisteína seja um fator de risco para doença microvascular cerebral são conflitantes, mas justificam maiores estudos. Estudos transversais e alguns longitudinais suportam a crescente prevalência de acidente vascular cerebral e demência vascular em indivíduos com hiper-homocisteinemia. As evidências de crescente neurodegeneração estão se acumulando. A relação com a depressão ainda é experimental, da mesma forma como com a epilepsia. Atualmente, estudos sobre tratamentos são necessários para colocar as evidências sobre bases mais sólidas. Os pacientes de alto risco também devem ser pesquisados para hiper-homocisteínemia, cujo tratamento deve ser feito com ácido fólico. Mais evidências são necessárias antes que pesquisas populacionais possam ser recomendadas.

Assessment of the role of hypephomccysteinemia and its metabolic consequences in the vascular access thrombosis among hemodialysis patients

The aim of this work was, to determine whether hyperhomocysteinemia and its metabolic consequences are associated with vascular access thrombosis in patients with end stage renal disease [ESRD], undergoing chronic hemodiahysis [HD]. This study included 3 groups. Group I: 15 ESRD patients on regular HD, with history of more than one episode of vascular access thrombosis. Group II: 15 ESRD patients on regular HD, with no episodes of vascular access thrombosis. Group III: 10 healthy, age and sex matched individuels as a control group. Plasma total homocysfeine [tHcy] and Von Willebrand Factor [vWF] were estimated by ELISA. Determination of plasma folate was done by Radioimmunoassay [RIA]. Plasma glutathione peroxidase activity was estimated by modified Paglia and Valentine method. Plasma methionine and cysteine levels were estimated by amino acid autoanalyser. plasma Hcy levels of both HD groups [GI and GII] were significantly higher than control groups [GIII] [F value = 44,487, P<0.0001], while no significant difference was found between GI and GII. Plasma folic acid levels of both patients' groups were significantly higher than control group [F value = 29.063, P<0.0001], while there was no significant difference between its level in GI and GII. Plasma vWF of HD patients with vascular access thrombosis [GI] was significantly higher than that of both GII and GIII and that of GII was significantly higher than GIII [F value = 62.010, P<0.0001]. Plasma glutathione peroxidase activity of both HD groups [GI and GII] was significantly lower than the control group [GIII] [F value = 69.446, P<0.0001], also its activity in patients with vascular access thrombosis [GI] was significantly lower than that of patients without vascular access thrombosis [GII]. Plasma cysteine and methionine levels of both HD groups were not significantly different from control group, also there was no significant difference in their levels between GI and GII. Plasma Hcy levels showed no significant correlation with number of vascular access thrombosis, whereas it showed a significant positive correlation with plasma vWF [r = 0.474, P<0.01] and negative correlation with plasma glutathione peroxidase activity [r = 0.643, P<0.0001]. From the previous study we concluded that: Hyperhomocyteinemia is not a direct cause of vascular access thrombosis. It is linked with increased plasma vWF levels. Endlothelial injury induced by hyperhomocysteinemia may be the cause. The lower levels of plasma glutathione peroxidase activity reflect increased oxidative stress induced by hyperhomocyteinemia in hemodialysis patients

Hiperhomocist(e)inemia: aterotrombosis y neurotoxidad

En esta revisión se describen las principales hormonas invlolucradas en el desarrollo y crecimiento muscular, haciendo especial énfasis en la hormona de cricimiento (GH) y los factores del crecimiento semejante a insulina (IGF). Se recopila la composición química, el lugar de síntesis y los principales mecanismos de acción de estas hormonas. Se observó que la GH, IGF, las hormonas tiroideas, la insulina, los glucocorticoides y los esteroides sexuales actuán en una forma compleja y coordinada para producir una respuesta productiva a diferentes estrategias nutricionales.