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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cysteine-homocysteine mixed disulphide, formed in the degradation of methionine, is detected routinely in the plasma of fasting patients homozygous for homocystinuria and in some obligate heteroxygotes. It has not hitherto been identified in the plasma of normal fasting man. Using a highly cross-linked resin with lithium citrate buffers on a JEOL. Amino Acid Analyser, we have detected the mixed disulphide in every one of the plasma samples from twenty normal fasting subjects. The mean concentration was 3.25 mumol/l (SD 0.85, N = 20), with a range of from 1.68 to 4.85 mumol/l. The other neutral and acidic amino acids were within the accepted normal range. The study shows that circulating homocysteine is normally not immediately transformed to cystathionine or remethylated to methionine; some combines with cysteine to form measurable amounts of mixed disulphide. Since homocysteine may produce endothelial damage, the present findings could be relevant to an understanding of the pathogenesis of vascular disease.
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PMID:The detection of cysteine-homocysteine mixed disulphide in plasma of normal fasting man. 10 Mar 23

We measured plasma sulphur amino acids in twenty-two patients with chronic renal failure and compared the findings with those obtained in twenty-two normal subjects. In fasting blood (08.00 hours) cysteine-homocysteine mixed disulphide was significantly increased in the renal patients, mean values (+/- SD) being 8.2 +/- 3.4 and 3.1 +/- 1.0 mumol/l respectively (P less than 0.001). The increase was positively correlated with reduced renal function, as assessed by serum creatinine (r = 0.62; P less than 0.01). Homocystine was detected in nineteen patients, the mean concentration (+/- SD) being 1.7 +/- 0.6 mumol/l; it was not found in any normal subject. Methionine levels were not different but there were significant increases in cystine (P less than 0.001) and taurine (P less than 0.05) in the patients. Similar values for these amino acids were found in a second blood sample drawn at 16.00 hours. Changes in the other neutral and acidic amino acids measured were in agreement with those reported in chronic azotaemia. We concluded that plasma levels of all the principal sulphur amino acids except methionine are elevated in chronic renal failure emphasizing the importance of the kidney in sulphur excretion. Prolonged accumulation of homocysteine and cysteine-homocysteine mixed disulphide may be relevant to the development of accelerated vascular disease in patients with chronic renal failure by producing endothelial damage.
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PMID:Sulphr containing amino acids in chronic renal failure with particular reference to homocystine and cysteine-homocysteine mixed disulphide. 11 20

Homocystinuria, an abnormality of methionine metabolism is associated with severe vascular disease in infancy and childhood. Homocysteine is formed during the metabolism of methionine and accumulations of this and of cysteine-homocysteine mixed disulfide in the plasma indicate a partial block in the methionine degradation pathway. Methionine metabolism was investigated in 25 patients aged under 50 with angiographically proved coronary artery disease and in 22 control patients, of whom 17 had normal coronary arteries at angiography and 5 were healthy volunteers. After an overnight fast, venous blood was drawn before and 4 h after oral L-methionine, 100 mg/kg. Plasma methionine levels at 4 h were not different in the two groups, but there were significant differences in the levels of cysteine-homocysteine mixed disulfide. This was detected in 5 of 22 in the noncoronary group and in higher concentration in 17 of 25 coronary patients (P less than 0-01). Age, weight, height, body-mass index, glucose tolerance, fasting serum urate, and triglycerides were not different, but serum cholesterol was higher in the coronary patients (P lessthan 0.01). These results suggest a reduced ability to metabolise homocysteine in some patients with premature coronary artery disease when this pathway is stressed.
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PMID:The pathogenesis of coronary artery disease. A possible role for methionine metabolism. 94 49

In order to clarify whether cystathionine beta-synthase (CBS) could differentiate groups of patients with various vascular diagnosis, CBS was studied in cultured human skin fibroblasts from 99 human subjects diagnosed as homozygotes or heterozygotes for CBS deficiency or suffering from atherosclerotic vascular disease or Down's syndrome (prone to less atherosclerosis). In addition, embryonic human skin fibroblasts and controls were analysed for CBS. We found significant group differences but the overlap in the hetero- and homozygotes for CBS deficiency was too extensive to allow any individual diagnosis based on cell culture studies. CBS activity was significantly lower in the atherosclerotic patients as compared to control subjects. The difference was mostly due to much higher CBS activity in the younger controls. Age dependency was markedly emphasized by very high values from embryonic cells. A strong negative correlation was noted for age and CBS activity in control subjects but not in the atherosclerotic patients. The results are important for the discussion of homocysteine in atherosclerosis and point to the importance of donor age on CBS activity in cultured cells. In addition, diagnosis of hetero-homozygosity for CBS activity is not possible on an individual basis by this method. Further studies in cell culture systems are needed to investigate if young patients (less than 45 years old) with atherosclerotic disease could be identified by low CBS activity in fibroblast cultures as indicated by this study.
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PMID:Age dependency of cystathionine beta-synthase activity in human fibroblasts in homocyst(e)inemia and atherosclerotic vascular disease. 138 57

The mechanism by which oral oestrogen-containing contraceptives in women and oestrogen treatment of prostatic carcinoma in men increases the risk of vascular disease is unclear. These agents decrease serum concentrations of vitamin B12, pyridoxal 5-phosphate, and folate, all of which are essential for the metabolism of the atherogenic amino acid homocysteine. We found serum vitamin B12 concentrations to be lower in 17 women using oral contraceptives (219 +/- 84 pmol l-1) than in 13 age-matched female controls (385 +/- 129, p less than 0.001), but similar values were obtained in the two groups both for fasting plasma homocysteine concentrations (9.1 +/- 2.4 vs 9.2 +/- 3.6 mumol l-1) and for the increase in these concentrations after methionine loading (19.2 +/- 7.5 vs 17.8 +/- 5.2 mumol l-1). In five men with prostatic carcinoma, high-dose oestrogen treatment decreased serum vitamin B12 concentrations by a mean of 30% (p less than 0.05) within 4 weeks, during which fasting plasma homocysteine concentrations decreased (13.8 +/- 4.5 vs 10.5 +/- 2.8 mumol l-1) and response to methionine loading increased (12.4 +/- 3.4 vs 17.3 +/- 5.1 mumol l-1), though the latter changes were non-significant. Our findings do not support the hypothesis that hyperhomocysteinemia explains cardiovascular risk in women using oral oestrogen-containing contraceptives, or in oestrogen-treated men with prostatic carcinoma.
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PMID:Plasma homocysteine in women on oral oestrogen-containing contraceptives and in men with oestrogen-treated prostatic carcinoma. 143 15

The interaction between plasma homocysteine levels and vitamins B6, B12, and folate is an exciting field and one that has gathered great momentum over the past few years, with the recognition that homocysteine probably plays an important role in occlusive vascular disease. Our understanding in this field is greatly advanced compared to just a few years ago. There are a number of important issues, however, that will need to be addressed in the future if we are to develop a sufficient knowledge base to effectively minimize the risk of occlusive vascular disease ascribable to hyperhomocysteinemia. These include (1) definitive evidence that homocysteine is the actual agent that mediates accelerated occlusive vascular disease and the mechanism by which this occurs; (2) an understanding of what constitutes a pathologic elevation in homocysteine (is there a threshold concentration in the plasma below which no vascular injury occurs? is the peak concentration achieved the critical determinant of injury, or is the area under the curve, or some other feature, more important?); (3) understanding what synergies might exist by adding B6 or B12 to a regimen of folate supplementation (what doses are most appropriate? will toxologic issues limit the utility of supplementation?); and (4) determining the circumstances where reduction of plasma homocysteine will retard or reverse the process of occlusive vascular disease.
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PMID:The effects of vitamins B12, B6, and folate on blood homocysteine levels. 144 25

The development of laboratory techniques for the culturing of vascular endothelial and smooth-muscle cells during the 1970s, followed by the rapid advances in molecular and cell biology during the 1980s, provided the foundation for the identification of growth factor and cytokine networks involved in maintenance of the normal vasculature as well as participating in diverse pathologic processes involving blood vessels. Vascular cells can produce and respond to a vast array of biochemical messengers that control cell replication, differentiation, and many specific cell functions. Investigators are beginning to explore the changes in the patterns of messengers exchanged between the vascular cells and infiltrating leukocytes during the initiation and progression of atherosclerosis. A variety of in vitro and in vivo studies have indicated that growth factors and cytokines that mediate the critical processes of inflammation and wound healing also play a central role in vascular disease. Indeed, many view atherosclerosis as the result of excessive or prolonged chronic inflammation and wound healing in response to diverse injurious stimuli to cells of the vessel wall. Vascular injury may result from many varied and interacting forces, including nutritional and metabolic abnormalities such as hyperlipidemias or elevated homocysteine, mechanical forces associated with hypertension, exogenous toxins including those found in cigarette smoke, abnormally glycated proteins associated with diabetes mellitus, oxidatively modified lipids or proteins, and, possibly, viral infections. Ultimately, a greater understanding of the activated cytokine and growth factor networks within the vascular wall following injury and during atherogenesis will allow clinical scientists to identify steps susceptible to therapeutic intervention using recombinant cytokines, antibodies, soluble receptors, or receptor antagonists. Other therapeutic strategies may involve the transfection of specific genes, which may inhibit atherosclerosis, into vascular cells at sites prone to lesion formation.
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PMID:Cytokines and growth factors in atherogenesis. 145 74

Depression among elderly people with reversible cognitive loss often manifests with concomitant vascular disease and can also precede the development of nonvascular degenerative dementia. Little is known about etiological factors for reversible or irreversible dementias in older depressed people. The amino acid homocysteine (HC), which is both a vascular disease risk factor and a precursor of the excitotoxic amino acids cysteine and homocysteic acid, could play a role in the pathophysiology of such individuals. Twenty-seven depressed elderly acute inpatients by DSM-III-R criteria had significantly higher plasma homocysteine levels and lower cognitive screening test scores than did 15 depressed young adult inpatients. HC was highest in the older patients who had concomitant vascular diseases (n = 14). HC was lowest in the older depressives who had neither vascular illnesses nor dementia (n = 8), comparable to the young adult depressives. Higher HC correlated significantly with poorer cognition only in the nonvascular geriatric patients (rs = -0.53). The findings extend earlier work showing higher HC in vascular patients from general medical populations, and also suggest a possible metabolic factor in certain dementias associated with late-life depression.
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PMID:Plasma homocysteine in vascular disease and in nonvascular dementia of depressed elderly people. 148 29

Hyperhomocysteinemia arising from impaired methionine metabolism, and usually due to a deficiency of cystathionine beta-synthase is a significant and independent risk factor for symptomatic vascular disease. It is not known if hyperhomocysteinemia in apparently healthy asymptomatic subjects is associated with atherosclerosis and whether such a relationship is independent of conventional risk factors. The prevalence of asymptomatic extracranial carotid artery atherosclerosis was determined by duplex ultrasound examination in 25 obligate heterozygotes with respect for cystathionine beta-synthase deficiency (whose children were known to be homozygous for this genetic defect) and in 21 controls. Hyperhomocysteinemia was determined by a standard methionine-loading test and conventional risk factors were also recorded. Twelve of 25 obligate heterozygotes and 8 of 21 normal controls had evidence of extracranial carotid artery atherosclerosis. Hyperhomocysteinemia as a genetic trait was not a significant risk marker, but the actual homocysteine level was associated with an increased risk of carotid disease. After adjustment for the effects of other significant risk factors, the odds ratio of hyperhomocysteinemia for carotid disease was 1.038 per unit increase in homocysteine level (P = 0.03). Hyperhomocysteinemia is a weak risk factor for asymptomatic extracranial carotid atherosclerosis and the relative risk associated with this genetic trait is less than that observed in a study of patients presenting with clinical manifestations of vascular disease.
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PMID:Hyperhomocysteinaemia: a risk factor for extracranial carotid artery atherosclerosis. 151 57

Serum level of the amino acid homocysteine, and vitamins folate, B12 and pyridoxal phosphate, and red blood cell folate levels were determined on Cycle days 3 and 21 in 26 women using the oral contraceptive Marvelon (30 mcg ethinyl estradiol and 150 mcg desogestrel), compared with 15 menstruating women. The 26 pill users had taken Marvelon for mean 3.7 years. Fasting homocysteine was assayed with an amino acid autoanalyzer; folate and B12 by radioimmunoassay; pyridoxal by high-performance liquid chromatography. The pill users had significantly higher homocysteine on Day 3 than controls (p0.01), levels comparable to those in heterozygote carriers of homocystinuria. Homocysteine levels were significantly lower in pill users on Day 21 compared to their levels on Day 3. Pyridoxal levels were significantly lower in Marvelon users on both days tested (p0.05). Homocysteine, folate and B12 were not significantly different in pill users and non-users on Day 21. The data indicate a cycle of high and low homocysteine levels in users of Marvelon. High homocysteine has been implicated in vascular disease, and may be a causative factor in the risk for thrombosis in pill users.
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PMID:Effects of sub-50 oral contraceptives on homocysteine metabolism: a preliminary study. 153 73


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