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)

With an improved highly reproducible method, we measured total plasma homocysteine (free plus protein-bound) and related amino acids in the fasting state in healthy subjects, before and after treatment with co-factors for homocysteine metabolism: 1 mg cyanocobalamin (n = 14), 5 mg folic acid (n = 13) or 40 mg pyridoxine hydrochloride (n = 15) daily for 14 days. Cyanocobalamin and pyridoxine hydrochloride had no effects on plasma levels of amino acids, but folic acid had a considerable homocysteine-lowering effect. Total plasma homocysteine was reduced in all but two subjects, from 19.9 +/- 4.4 (mean +/- SEM) to 9.5 +/- 1.0 mumol/l (-52%, p less than 0.01). We propose that folic acid in excess acts by enhancing the remethylation of homocysteine to methionine. The finding confirms a previous report by us. Since homocysteine is considered to be an atherogenic amino acid and recent reports suggest that mild to moderate homocysteinaemia is also associated with premature vascular disease, treatment with folic acid might be of use as prophylaxis.
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PMID:Folic acid--an innocuous means to reduce plasma homocysteine. 337 78

To explore interrelations between folic acid and methionine metabolism in chronic renal insufficiency, we measured plasma amino acids in 21 patients with mean serum creatinine +/- SD of 560 +/- 240 mumol/L, after a ten-hour overnight fast, before and after administration of 5 mg of oral folic acid daily for 15 +/- 6 days. Mean plasma homocysteine was 12.9 +/- 6.8 mumol/L in the patients and 4.2 +/- 0.8 mumol/L in 24 normal controls (P less than .001), and after folic acid administration it declined in the patients to 6.8 +/- 2.8 mumol/L (P less than .0001) in linear proportion (r = .92) to the prefolate homocysteine level. Methionine concentrations were normal in the patients and did not change after folate administration, nor did elevated cysteine and creatinine. Plasma serine was lower (88.3 +/- 17.2 v 121 +/- 25 mumol/L, P less than .41) and declined further to 67.8 +/- 16.4 (P less than .0001) after folate, while prefolate glycine levels increased from 273.3 +/- 61.2 to 313.2 +/- 97.5 mumol/L (P less than .01). Serum and red-cell folate levels were normal in the patients before treatment. The results show that homocysteine levels are increased in chronic renal insufficiency, but may be lowered by folate enhancement of remethylation of homocysteine to methionine. Since elevated plasma homocysteine is associated with premature vascular disease, folic acid may reduce cardiovascular risk in chronic renal insufficiency.
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PMID:Folic acid lowers elevated plasma homocysteine in chronic renal insufficiency: possible implications for prevention of vascular disease. 338 35

Premature arteriosclerosis and thromboembolic events are well-known complications of homozygous homocystinuria due to cystathionine synthase deficiency. It is unknown whether heterozygosity for homocystinuria predisposes to premature vascular disease. We explored the frequency of excessive homocysteine accumulation after standardized methionine loading in 75 patients presenting with clinical signs of ischemic disease before the age of 50:25 with occlusive peripheral arterial disease, 25 with occlusive cerebrovascular disease, and 25 with myocardial infarction. In seven patients in each of the first two groups but in none of the patients in the third group, heterozygosity for homocystinuria was established on the basis of pathological homocysteinemia after methionine loading and cystathionine synthase deficiency in skin fibroblast cultures. Because the frequency of heterozygosity for homocystinuria in the normal population is 1 in 70 at the most, we conclude that this condition predisposes to the development of premature occlusive arterial disease, causing intermittent claudication, renovascular hypertension, and ischemic cerebrovascular disease.
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PMID:Heterozygosity for homocystinuria in premature peripheral and cerebral occlusive arterial disease. 188 23

Premenopausal women develop occlusive artery disease less frequently than postmenopausal women. In coronary heart disease, higher blood levels of homocysteine-cysteine mixed disulphide have been reported. Therefore, in healthy subjects, we studied the role of menopausal status in the transsulphuration of methionine in 10 premenopausal and 10 postmenopausal women. To exclude the role of aging, we compared these results with those in 10 younger and 10 older men of comparable age groups. An oral methionine load (0.1 g/kg of body weight) was administered after overnight fasting. Before and during 8 h, thereafter, serum levels of methionine, homocystine, and homocysteine-cysteine mixed disulphide were measured. In the fasting state, serum methionine levels were similar in the premenopausal women and both groups of men. Postmenopausal women had significantly lower fasting levels. Peak levels and clearances of methionine after loading did not differ between the groups. In the fasting state, homocystine was never detectable; yet, after methionine loading, slight homocystinemia was present in 12 out of 20 men, and was more pronounced in all postmenopausal women. However, homocystinemia did not occur in any of the premenopausal women after loading. Fasting serum homocysteine-cysteine mixed disulphide levels did not differ between both groups of men and postmenopausal women. In premenopausal women, both fasting and postloading disulphide levels were significantly lower than in any other group. We conclude that premenopausal women have a unique efficiency of methionine handling, and thereby are preserved against the accumulation of homocysteine after methionine loading. We speculate that this phenomenon might account for the lower incidence of vascular disease in women in the reproductive life cycle.
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PMID:Unique efficiency of methionine metabolism in premenopausal women may protect against vascular disease in the reproductive years. 664 82

Thrombosis is a well-recognized complication of atherosclerosis and may be a factor in initial lesion formation. Experimental endothelial cell injury results in activation of the coagulation mechanism and therefore may be a critical aspect of the pathogenesis of occlusive vascular disease. If this is so, then risk factors for atherosclerosis should affect the endothelium either by causing cell injury, inhibiting repair mechanisms, or altering its thromboresistant properties. To test this, we studied the effect of several risk factors on endothelial cell behavior in vitro. Since the smooth muscle cell is the major cellular component of human atherosclerotic plaque and since a primary smooth muscle cell lesion is suggested by the clonal nature of human plaque, we also studied the effect of risk factors on arterial smooth muscle behavior. We have found that homocysteine directly injures human endothelium, which may account for the premature arterial disease in homocystinuria. Serum from patients with familial hypercholesterolemia inhibits the critical function of endothelial cell migration, as well as arterial smooth muscle cell migration. Moderate hypoxia has no effect on endothelial cell or smooth muscle cell viability, proliferation, or migration. Platelet factors are shown to affect human smooth muscle cell proliferation and both endothelial cell and smooth muscle cell migration. Preliminary study of platelet activation in diabetes with retinopathy suggests a relation to glucose control, but might reflect underlying vessel disease rather than direct platelet effect.
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PMID:Studies on the cellular basis of atherosclerosis: the effects of atherosclerosis risk factors on platelets and the vascular endothelium. 729 72

The objective of this study was to examine if hyperhomocysteinemia is associated with occlusive vascular disease in hemodialysis patients. The study design included risk factor analysis and determination of serum homocysteine in hemodialysis patients. Fifty chronic uremic patients on regular hemodialysis treatment were studied. Twenty-four patients had coronary, cerebral, or peripheral signs of occlusive vascular disease. Cerebral vascular disease was diagnosed by computed tomography, arterial angiography, or Doppler sonography of the carotid and vertebral arteries. Coronary vascular disease was diagnosed by documented history of myocardial infarction or by coronary angiography. The diagnosis of peripheral vascular disease was established by angiography of the lower limb arteries. In all control patients, Doppler sonography of the carotid, vertebral, and lower limb arteries and thallium-201 exercise imaging were without pathologic results. Measurements included blood pressure, body mass index, smoking behavior, serum homocysteine (measured by gas chromatography/mass spectrometry), serum total, low-density lipoprotein, and high-density lipoprotein cholesterol, lipoprotein (a), triglycerides, and plasma fibrinogen. In a stepwise multiple logistic regression analysis, high serum homocysteine was significantly associated with occlusive arterial disease (R = 0.23; P = 0.031). Furthermore, hypertension (R = 0.18; P = 0.058), but not serum total, low-density lipoprotein, and high-density lipoprotein cholesterol, lipoprotein (a), triglycerides, diabetes mellitus, body mass index, plasma fibrinogen, and smoking behavior, was significantly associated with atherosclerosis. Our results support the hypothesis that hyperhomocysteinemia is an independent risk factor for vascular disease in hemodialysis patients.
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PMID:Hyperhomocysteinemia and the risk for vascular disease in hemodialysis patients. 757 64

Homocyst(e)ine [H(e)], the sum of homocysteine, homocystine, and the homocysteine-cysteine mixed disulfide, free and protein-bound, has been shown to be associated in retrospective case control studies, and in one prospective study, with vascular disease, including coronary artery disease (CAD), cerebrovascular disease, and peripheral vascular disease. Elevated levels of homocyst(e)ine severe enough to cause homocystinuria are seen in severe nutritional deficiencies of vitamin B12, folic acid and vitamin B6. Rare genetic disorders of vitamin B12 synthesis of 5'-10'-methylene tetrahydrofolate reductase, or the pyridoxal phosphate-dependent enzyme cystathionine beta-synthase may cause severe hyperhomocyst(e)inemia and homocystinuria. The clinical manifestation of these disorders are mental retardation, neurological disorders, and widespread thromboembolic phenomena. The measurement of H(e) is currently performed using high-pressure liquid chromatography with fluorescence detection. Other methods, especially mass spectroscopy, are also used. Internal standards using increasing concentrations of homocystine and acetylcysteine and several external standards are used to ensure accuracy of the assay. Milder elevations of H(e) have recently been associated with vascular disease, in both men and women. The strength of this association appears to be stronger for peripheral and cerebrovascular disease than for CAD. Nevertheless, several case control studies in Europe, Canada, and the United States have shown that H(e) levels are elevated in CAD patients compared with controls, and H(e) levels are independent of the conventional cardiovascular risk factors (age, gender, lipid and lipoprotein cholesterol levels, hypertension, or cigarette smoking). One prospective study, the Physicians' Health Study, has shown that H(e) levels are slightly but significantly higher in CAD cases vs controls in a population of US physicians.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Measurement of homocyst(e)ine in the prediction of arteriosclerosis. 762 74

Hyperhomocysteinaemia has been identified as a risk factor for cerebrovascular, peripheral vascular and coronary heart disease. Elevated levels of plasma homocysteine can result from genetic or nutrient-related disturbances in the trans-sulphuration or re-methylation pathways for homocysteine metabolism. 5, 10-Methylenetetrahydrofolate reductase (MTHFR) catalyzes the reduction of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the predominant circulatory form of folate and carbon donor for the re-methylation of homocysteine to methionine. Reduced MTHFR activity with a thermolabile enzyme has been reported in patients with coronary and peripheral artery disease. We have identified a common mutation in MTHFR which alters a highly-conserved amino acid; the substitution occurs at a frequency of approximately 38% of unselected chromosomes. The mutation in the heterozygous or homozygous state correlates with reduced enzyme activity and increased thermolability in lymphocyte extracts; in vitro expression of a mutagenized cDNA containing the mutation confirms its effect on thermolability of MTHFR. Finally, individuals homozygous for the mutation have significantly elevated plasma homocysteine levels. This mutation in MTHFR may represent an important genetic risk factor in vascular disease.
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PMID:A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. 764 79

Several studies have shown a relation between hyperhomocysteinaemia and arterial vascular disease. We looked at the association between hyperhomocysteinaemia and venous thrombosis which could be clinically important as hyperhomocysteinaemia is easily corrected by vitamin supplementation. We studied 185 patients with a history of recurrent venous thrombosis and 220 controls from the general population. Homocysteine concentrations were measured before and 6 h after oral methionine loading. We defined hyperhomocysteinaemia as the homocysteine concentration above the fasting or the postmethionine value found for the 90th percentile of the controls. Of the 185 patients with recurrent thrombosis, 46 (25%) had fasting homocysteine concentrations above the 90th percentile or the controls (odds ratio is 3.1 [1.8-5.5]). After adjustment for age, sex, and menopausal status the odds ratio was 2.0 (1.5-2.7). Similar results were found for the post-methionine value (unadjusted odds ratio 3.1 [1.7-5.5], adjusted 2.6 [1.9-3.5]). Hyperhomocysteinaemia is a common risk factor for recurrent venous thrombosis and can lead to a two-fold or three-fold increase in risk.
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PMID:Is hyperhomocysteinaemia a risk factor for recurrent venous thrombosis? 760 2

Elevated total homocysteine (Hcy) in plasma is an independent risk factor for early-onset vascular disease in the coronary, cerebral, and peripheral arteries. Different forms of Hcy, and their relation to other aminothiols in plasma, have not been investigated in patients with vascular disease. We therefore investigated 65 patients (35 men and 30 women) operated on for peripheral arterial disease at < 50 years of age and 65 age- and sex-matched control subjects. Total, reduced, oxidized, and protein-bound Hcy, cysteine (Cys), and cysteinylglycine (CysGly) were measured 0 to 11 years (mean, 6 years) postoperatively, in the fasting state, and after a standard methionine loading dose that caused a transient increase in reduced, oxidized, and protein-bound Hcy. All forms of Hcy and Cys, except reduced Cys, were higher in fasting patients than fasting control subjects. A similar difference between the groups was observed after methionine loading. The levels of most Hcy forms both during fasting and after methionine loading were related to smoking, but multivariate analysis showed that the difference between patients and control subjects could not be explained by smoking alone. Notably, reduced Cys and the reduced/total ratio for Cys were significantly higher in control subjects than in patients, both during fasting and after methionine loading. In both groups, the redox status and protein binding of the various aminothiols in plasma were interactive, as demonstrated by positive correlations between their reduced/total ratios and by a decrease in protein-bound Cys when protein-bound Hcy was elevated during methionine loading.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Redox status and protein binding of plasma homocysteine and other aminothiols in patients with early-onset peripheral vascular disease. Homocysteine and peripheral vascular disease. 774 31


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