Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperhomocysteinaemia is a risk factor for premature atherosclerosis and venous thromboembolic disease. Supplementation with folic acid and vitamin B6 has been shown to decrease plasma homocysteine but data fail to assess an effect on the progression of vascular disease. We measured plasma homocysteine and two markers of endothelial injury (plasma soluble thrombomodulin and von Willebrand factor) at baseline and after 3 months of treatment with folic acid and vitamin B6. After this treatment there was a significant decrease in fasting soluble thrombomodulin (-15 ng/ml, 95%CI 5-22.2). Von Willebrand factor was significantly raised after methionine load at baseline but did not significantly rise after supplementation.
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PMID:Three months supplementation of hyperhomocysteinaemic patients with folic acid and vitamin B6 improves biological markers of endothelial dysfunction. 1060 84

Evidence of the importance of the B vitamins folic acid, vitamin B-12, and vitamin B-6 for the well-being and normal function of the brain derives from data showing neurologic and psychologic dysfunction in vitamin deficiency states and in cases of congenital defects of one-carbon metabolism. The status of these vitamins is frequently inadequate in the elderly and recent studies have shown associations between loss of cognitive function or Alzheimer disease and inadequate B vitamin status. The question that arises is whether these B vitamin inadequacies contribute to such brain malfunctions or result from aging and disease. From a theoretical standpoint, these inadequacies could give rise to impairment of methylation reactions that are crucial to the health of brain tissue. In addition or perhaps instead, these inadequacies could result in hyperhomocysteinemia, a recently identified risk factor for occlusive vascular disease, stroke, and thrombosis, any of which may result in brain ischemia. Advances in the understanding of this putative relation between inadequate vitamin status and loss of cognitive function in the elderly are likely to be slow and may depend on the outcomes of both prospective studies and longitudinal studies in which nutritional intervention is provided before cognitive decline occurs.
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PMID:B vitamins, homocysteine, and neurocognitive function in the elderly. 1112 62

This article discusses the metabolism of homocysteine, factors affecting its plasma level, and the evidence for its role in the pathogenesis of vascular disease. The treatment of hyperhomocysteinemia and its possible impact on vascular disease prevention and progression are described also.
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PMID:Homocysteine, B vitamins, and coronary artery disease. 1068 36

Hyperhomocysteinemia is a risk factor for vascular disease, although its mechanism of action is not fully clear. Different experimental studies have suggested that homocysteine (Hcy) exerts a pro-oxidant effect in the presence of metal ions (Fe and Cu). To test for a similar effect in vivo, we studied plasma markers of lipid and protein oxidation during hyperhomocysteinemia induced by an oral methionine load. Twenty-nine subjects (aged 61 +/- 25 years; 17 women), 25 of whom underwent oral methionine (100 mg/kg) loading, were studied; in every case, we measured total plasma Hcy, malondialdehyde (MDA), conjugated dienes (DIE), and oxidized protein ([PTOX] carbonylic groups) in basal conditions and 4, 6, 8, and 24 hours after methionine loading. Four participants acted as controls. In every case, we also measured total plasma antioxidant capacity (ANTOX) in basal conditions and 8 hours after methionine loading. Eight hours after methionine loading, plasma Hcy increased from 17.6 +/- 11.4 to 54.3 +/- 31.6 nmol/mL, PTOX from 0.33 +/- 0.18 to 0.71 +/- 0.33 nmol/mg protein, DIE from 493 +/- 163 to 590 +/-202 optical density units, and MDA from 1.66 +/- 0.81 to 2.1 +/- 0.93 nmol/mL. There was a significant correlation (Spearman's r) between Hcy and both PTOX (r = .86, P = .01) and MDA (r = .47, P < .05) 8 hours after methionine loading. No significant modifications of the plasma parameters were found during the observation period in controls. ANTOX at 8 hours was significantly (paired ttest) reduced in probands (from 1.74 +/- 0.59 to 1.14 +/- 0.55 mmol/mL, P = .014); no significant difference was observed for plasma ANTOX in controls. Hyperhomocysteinemia due to oral methionine loading induced an increase in plasma oxidation markers. In the absence of hyperhomocysteinemia, no significant modifications were observed. These findings, together with the decrease in ANTOX and the corresponding increase in total plasma Hcy, are consistent with a pro-oxidant effect of acute hyperhomocysteinemia in vivo.
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PMID:Peroxidation indices and total antioxidant capacity in plasma during hyperhomocysteinemia induced by methionine oral loading. 1069 Sep 49

It is proposed that chronic moderate hyperhomocysteinemia has a causal role in a number of common diseases of late life, including occlusive vascular disease, cognitive decline, senile osteoporosis and presbyopia. These diseases are seen as clinical counterparts of the main manifestations of homocystinuria (vascular occlusions of arteries and veins, mental retardation, osteoporosis and ectopia lentis, respectively) that develop only after many years of exposure to moderately elevated homocysteine (Hcy) levels. The multisystem toxicity of Hcy is attributed to its spontaneous chemical reaction with many biologically important molecules, primarily proteins. The formation of these Hcy-adducts is dependent on time and Hcy concentration and leads to loss or diminution of function of the derivatized molecules. Irreversible homocysteinylation of long-lived proteins should lead to cumulative damage and progressive clinical manifestations. Fibrillin 1 is seen as the paradigm of extracellular connective tissue proteins that are specially susceptible to Hcy (and presumably Hcy thiolactone) attack. The prominent presence of epidermal growth factor (EGF)-like domains in fibrillin and in many other extracellular proteins of the coagulation, anticoagulation, and lipoprotein transport pathways, all of which malfunction in hyperhomocysteinemia, suggests that EGF-like domains may be preferential sites of homocysteinylation.
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PMID:Mechanisms of homocysteine toxicity on connective tissues: implications for the morbidity of aging. 1072 8

Hyperhomocysteinemia, which results from renal impairment, may promote arteriosclerosis and glomerulosclerosis. The combined effect of renal failure and a common mutation (C677T) in the methylenetetrahydrofolate reductase gene that leads to serum homocysteine elevations in dialysis patients was investigated. Genotypes were determined at this locus in 545 dialysis patients and 676 healthy subjects, and serum concentrations of total homocysteine and folate were measured in a subgroup of 464 patients. Multiple regression analysis showed that the TT genotype and low serum folate concentration were independent positive predictors of the serum total homocysteine concentration. The negative slope of a regression line relating homocysteine and folate concentrations was significantly steeper for patients with the TT genotype than for other genotypes. Patients with the TT genotype were significantly younger at the time of the study (54.8 +/- 12.9 versus 59.6 +/- 12.3 yr; P < 0.0001) and at initiation of dialysis (46.6 +/- 16.2 versus 51.2 +/- 15.9 yr; P < 0.02) than those with other genotypes. In patients who were older at the time of the study or at initiation of dialysis, the prevalence of the TT genotype was lower than in control subjects. In the middle quartiles (37.1 to 63.0 yr) for age at the start of dialysis, the prevalence of the TT genotype was lower in patients with a longer duration of dialysis. In this cross-sectional study, genotype and serum total homocysteine concentration were not independent risk factors for vascular disease in dialysis patients. These results indicate that the methylenetetrahydrofolate reductase mutation is a significant independent predictor for serum total homocysteine concentration.
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PMID:The C677T methylenetetrahydrofolate reductase gene mutation in hemodialysis patients. 1077 Sep 66

We hypothesized that elevated plasma homocysteine concentrations (hyperhomocysteinemia) exist in patients receiving antiepileptic drugs (AED), and a long-term administration of AED may result in an increased risk of occlusive vascular disease in these patients. A total of 62 patients who received AED monotherapy (phenytoin, lamotrigine, carbamazepine or valproate) participated in this study. Blood concentrations of homocysteine, folate, vitamin B-12 and pyridoxal-5'-phosphate (PLP, a coenzyme form of vitamin B-6) were measured, and thermolabile genotypes of 5, 10-methylenetetrahydrofolate reductase (MTHFR) were also determined. Of 62 patients, only seven (11.4%) had hyperhomocysteinemia. Of 20 patients who received phenytoin, three (15.0%) had hyperhomocysteinemia, whereas 85% of these had plasma folate concentrations below the normal range. However, erythrocyte folate concentrations were abnormally low in only 25% of the patients who received phenytoin. Valproate administration increased serum vitamin B-12 concentrations. Over 55% of the entire patients had PLP concentrations below the normal range, although the reason is unknown. Only three patients had the homozygous thermolabile genotype of MTHFR; therefore, meaningful statistical analysis was not possible in this study. However, one patient with homozygous genotype who received phenytoin therapy had hyperhomocysteinemia with poor folate nutritional status, and the other two had normal homocysteine concentrations with normal folate status. Our data suggest that hyperhomocysteinemia is not a serious clinical concern in epileptic patients when folate nutriture is adequate.
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PMID:Homocysteine, folate, vitamin B-12 and vitamin B-6 in patients receiving antiepileptic drug monotherapy. 1077 Dec 53

S-Adenosylhomocysteine, a potent intracellular methylation inhibitor, is suggested as a potential mediator for hyperhomocysteinemia-related vascular changes. We investigated the effect of acute and chronic hyperhomocysteinemia on intracellular S-adenosylhomocysteine and S-adenosylmethionine in rats and humans. Elevated plasma homocysteine in rats infused with homocysteine produced an increase in S-adenosylhomocysteine (P < 0.001) but not S-adenosylmethionine levels (P > 0.05) in various rat tissues. However intraerythrocyte S-adenosylhomocysteine and S-adenosylmethionine levels were not changed in homocysteine-infused rats and human subjects with experimentally acute hyperhomocysteinemia by methionine loading test. In contrast, erythrocyte S-adenosylhomocysteine levels were significantly higher in chronic renal failure patients, who had chronically elevated plasma homocysteine levels, than in either vascular disease patients or healthy controls (P < 0.05). In conclusion, acute hyperhomocysteinemia can increase intracellular S-adenosylhomocysteine levels in tissues actively involved in homocysteine metabolism. The findings are relevant to homocysteine-related endothelial dysfunction since S-adenosylhomocysteine modulates endothelial cell apoptosis.
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PMID:Interrelations between plasma homocysteine and intracellular S-adenosylhomocysteine. 1077 79

Homocysteine results from the demethylation of the essential amino acid methionine. Its metabolism depends primarily on three enzymes and several vitamin cofactors (vit. B6, B9 and B12). Genetic abnormality in these enzymes or deficiency of these vitamins lead to Hyperhomocysteinemia. Hyperhomocysteinemia belongs among the congenital thrombophilies and is a long-known vascular disease risk factor. The discovery that hyperhomocysteinemia may also be responsible for several pregnancy complications has only recently been made. Studies in this area are still scarce and report on limited numbers of patients. It nevertheless appears clear that HHCh is associated with the syndromes of repeated miscarriage, pre-eclampsia, placenta abruptio, thromboembolic events, neural tube defects, and perhaps with fetal death-in-utero and intra-uterine growth retardation. Supplementation with vitamin B9 can reduce plasma HC levels, and is thus recommended in patients with HHCh. The prevention of thromboembolic events during pregnancy by anticoagulant treatment is also desirable in these patients.
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PMID:[Hyperhomocysteinemia and pregnancy: a dangerous association]. 1084 24

Mild hyperhomocysteinemia has been considered a cardiovascular risk factor. However, recent prospective studies have not demonstrated that hyperhomocysteinemia or the underlying genetic defect on methylentetrahydrofolate reductase is associated with a higher risk of coronary or peripheral artery disease. We compared serum homocysteine, folate, and vitamin B(12) levels of patients with coronary and peripheral vascular disease with those of age- and sex-matched healthy individuals. Subjects taking multivitamins, with diabetes mellitus, or serum creatinine levels over 1.5 mg/dL were excluded from the study. Homocysteine was measured by fluorimetric high-performance liquid chromatography. Serum folate and vitamin B(12) levels were measured by an ion-capture method. We studied 32 patients with peripheral vascular disease (10 female), aged 69.6 +/- 11 y, 24 age- and sex-matched control subjects, 52 patients with coronary artery disease (7 female), aged 59.5 +/- 10.4 y, and 42 age- and sex-matched control subjects. Serum homocysteine levels were 11.7 +/- 7.4 and 9.3 +/- 4.5 micromol/L in vascular patients and in the control counterparts, respectively (not significant). The levels for coronary patients and the control counterparts were 9.0 +/- 3.9 and 8.6 +/- 3.6 micromol/L, respectively (not significant). Folate levels were 4.48 +/- 2.42 and 7.14 +/- 4.04 ng/mL in vascular patients and control subjects, respectively (P < 0.02); the levels in coronary patients and control counterparts were 5.15 +/- 1.9 and 6.59 +/- 2.49 ng/mL, respectively (P < 0.01). No differences in vitamin B(12) or tocopherol levels were observed between patients and control subjects. There were no differences in homocysteine levels, but lower serum folate levels were observed when comparing patients with atherosclerotic vascular disease and healthy control subjects.
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PMID:Low serum folate but normal homocysteine levels in patients with atherosclerotic vascular disease and matched healthy controls. 1086 99


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