Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Homocysteine (HCY), which is derived from the intracellular metabolism of methionine, is exported into plasma, where it circulates mostly in oxidized forms (i.e., homocystine and cysteine-HCY disulfide) and mainly bound to proteins. Concentrations of total HCY, or homocyst(e)ine [H(e)], are increased in 15-40% of patients with coronary, cerebral, or peripheral arterial diseases. Such association of H(e) with arterial occlusive diseases has been documented in retrospective, cross-sectional, and prospective studies. Concentrations of H(e) are also increased in subjects having thickened carotid arteries, as determined by ultrasonography, and who are asymptomatic for atherosclerosis. Statistical analyses of data from several series of patients demonstrate that H(e) concentrations are associated with coronary artery disease, independently from most other risk factors for atherosclerosis. The increased concentrations of H(e) are readily corrected by folic acid, occasionally supplemented with pyridoxine, vitamin B12, choline, or betaine. Whether these supplements affect the evolution of atherosclerotic disease needs to be established by prospective, placebo-controlled clinical trials.
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PMID:Plasma homocyst(e)ine and arterial occlusive diseases: a mini-review. 781 76

Atherosclerosis is a leading cause of death and disability in the Western world, and an important risk factor for it may be an elevated level of the plasma amino acid homocysteine. The biochemical characteristics of homocysteine, along with historical, laboratory, and clinical evidence for its pathologic role in atherosclerosis, are reviewed. Possible therapies for reducing elevated homocysteine levels and the possible impact of therapy in atherosclerosis are examined.
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PMID:Importance of elevated plasma homocysteine levels as a risk factor for atherosclerosis. 794 99

The aim of this study was to determine the prevalence of hyperhomocysteinaemia in cardiac transplant recipients. Three groups of subjects were studied: 27 heart transplant recipients, 14 to 63 months (mean = 36.5) after transplantation; 10 patients with moderate chronic renal insufficiency without clinical evidence of vascular disease; 17 apparently healthy individuals. Twenty-five out of 27 transplanted patients had a coronaroangiography within 6 months of homocysteine measurement. Plasma homocysteine was measured both while the subject was fasting (t0) and 6 h after administration of 0.1 g.kg-1 of methionine (t6). Hyperhomocysteinaemia was present in 14/27 fasting transplanted patients and after methionine loading. Mean plasma levels of homocysteine at t0 were higher (P = 0.03) in transplanted heart recipients (15.4 +/- 7 mumol.l-1) than in the renal patients (9.9 +/- 5 mumol.l-1) despite similar mean plasma creatinin. In eight transplanted patients with angiographic coronary abnormalities of the cardiac graft, homocysteinaemia was at t0 17.1 +/- 9 mumol.l-1 and at t6 47.8 +/- 25 mumol.l-1. In 17 transplanted patients with angiographically normal coronary arteries, plasma homocysteine levels were at t0, 13.2 +/- 4 mumol.l-1 and at t6, 46.8 +/- 25 mumol.l-1. We conclude that hyperhomocysteinaemia is common in transplanted heart recipients, and partly related to renal insufficiency. No correlation was found between hyperhomocysteinaemia and angiographic evidence of coronary atherosclerosis of the graft, but the population of the study was possibly too small to establish this correlation.
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PMID:Hyperhomocysteinaemia in heart transplant recipients. 798 18

Homocysteine is a thiol-containing amino acid resulting from demethylation of methionine. The free and protein-bound forms of the amino acid and derived disulfides are called homocyst(e)ine [H(e)]. Multiple studies have shown elevated H(e) levels in patients with coronary, cerebrovascular, or peripheral arterial diseases; this association is frequent and independent of most other risk factors for atherosclerosis. In the 1993 Frontiers in Medicine Symposium investigators discussed the genetic, physiological, nutritional, and pharmacological mechanisms involved in the regulation of plasma H(e), the association of H(e) with arterial occlusive diseases, and the relationships of H(e) with nitric oxide and haemostasis. High plasma H(e) levels usually can be reversed with vitamin supplements. Whether vitamin supplements will affect the evolution of arterial occlusive diseases needs to be established in prospective, placebo-controlled, randomized, clinical trials.
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PMID:Homocyst(e)ine and arterial occlusive diseases. 798 96

It has been shown that hyperhomocysteinemia is a risk factor for atherosclerotic vascular disease. In this study, we measured total plasma homocysteine in continuous ambulatory peritoneal dialysis (CAPD) patients and evaluated its correlation with atherosclerosis. Subjects consisted of healthy volunteers, and hemodialysis (HD) and CAPD patients. Fluoro-HPLC was employed to estimate plasma levels of total homocysteine (Hcy). Plasma levels of total Hcy were significantly higher in the CAPD patients compared with the HD patients and controls. Atherosclerotic score (ASS) was calculated, and the correspondence with plasma levels of total Hcy was analyzed. There was a significant correlation between plasma levels of total Hcy and ASS in CAPD patients. However, plasma levels of total Hcy did not correlate with age, plasma vitamin B6 level, residual renal function, protein catabolic rate (PCR), or KT/V. Our present study suggests that elevated concentrations of total plasma Hcy might play a role in the development of atherosclerosis in CAPD patients.
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PMID:Hyperhomocysteinemia as a possible role for atherosclerosis in CAPD patients. 799 46

Homocysteine induced toxicity has been examined in cultures of human umbilical vein endothelial cells. The toxic effects of the amino acid alone and the amino acid plus Cu2+ could be prevented by catalase and decreased by desferal, when either was present in the culture medium. When desferal was allowed to accumulate intracellularly, no significant protection from homocysteine induced toxicity was observed. Even though lipid peroxidation accompanied the toxicity induced by homocysteine and homocysteine plus Cu2+, inhibition of lipid peroxidation in either case had no effect on cell viability. The significance of these results is discussed.
Atherosclerosis 1994 Feb
PMID:Lipid peroxidation and homocysteine induced toxicity. 800 92

The relation of serum total homocysteine and lipoprotein(a) (Lp(a)) with the incidence of atherosclerotic disease was investigated among 7424 men and women aged 40-64 years free of atherosclerotic disease at baseline in 1977. During the 9-year follow-up, 134 male and 131 female cases with either myocardial infarction or stroke were identified. For each case a control subject was selected belonging to the same sex and 5-year age group. Serum samples collected in 1977 were stored at -20 degrees C and analyzed in 1991. The mean serum homocysteine concentration of male cases and controls was 9.99 mumol/l and 9.82 mumol/l at baseline and that of female cases and controls 9.58 mumol/l and 9.24 mumol/l, respectively. The median serum Lp(a) concentration of male cases and controls was 73 mg/l and 108 mg/l and that of female cases and controls 113 mg/l and 91 mg/l, respectively. The differences between cases and controls were not statistically significant. There was also no significant association between either homocysteine or Lp(a) and atherosclerotic disease, myocardial infarction or stroke in logistic regression analyses. The odds ratios varied from 1.00 to 1.26 for homocysteine and from 0.81 to 1.06 for Lp(a). The results of this prospective population-based study do not support the hypotheses that serum homocysteine or Lp(a) are risk factors for atherosclerotic disease. The lack of association between serum homocysteine and atherosclerotic disease may be due to the exceptionally low gene frequency predisposing to homocysteinemia in Finland.
Atherosclerosis 1994 Mar
PMID:Relation of serum homocysteine and lipoprotein(a) concentrations to atherosclerotic disease in a prospective Finnish population based study. 801 11

Plasma homocysteine levels are elevated in 20-30% of all patients with premature atherosclerosis. Although elevated homocysteine levels have been recognized as an independent risk factor for myocardial infarction and stroke, the mechanism by which these elevated levels cause atherosclerosis is unknown. To understand the role of homocysteine in the pathogenesis of atherosclerosis, we examined the effect of homocysteine on the growth of both vascular smooth muscle cells and endothelial cells at concentrations similar to those observed in clinical studies. As little as 0.1 mM homocysteine caused a 25% increase in DNA synthesis, and homocysteine at 1 mM increased DNA synthesis by 4.5-fold in rat aortic smooth muscle cells (RASMC). In contrast, homocysteine caused a dose-dependent decrease in DNA synthesis in human umbilical vein endothelial cells. Homocysteine increased mRNA levels of cyclin D1 and cyclin A in RASMC by 3- and 15-fold, respectively, indicating that homocysteine induced the mRNA of cyclins important for the reentry of quiescent RASMC into the cell cycle. Furthermore, homocysteine promoted proliferation of quiescent RASMC, an effect markedly amplified by 2% serum. The growth-promoting effect of homocysteine on vascular smooth muscle cells, together with its inhibitory effect on endothelial cell growth, represents an important mechanism to explain homocysteine-induced atherosclerosis.
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PMID:Promotion of vascular smooth muscle cell growth by homocysteine: a link to atherosclerosis. 802 89

Interest in total plasma homocysteine (homocyst[e]ine) as a risk factor for atherosclerosis is expanding. However, the origin of plasma homocyst(e)ine has not been defined. Our studies examined the metabolism of homocyst(e)ine by blood cells as a potential contributor to the homeostasis of homocyst(e)inemia. Incubation of blood for 24 hours at 37 degrees C produced a threefold increase in the level of plasma homocyst(e)ine. In samples of fractionated blood cells incubated in vitro, increases in total plasma homocysteine were limited to incubated erythrocyte fractions and were influenced by addition of methionine. Anticoagulants had no significant effect. Incubation of blood in the presence of methionine tagged with sulfur 35 demonstrated incorporation of label into homocysteine and transsulfuration products. Similar incubations of blood cell fractions suggested that synthesis of homocysteine occurred in erythrocytes, whereas leukocytes both synthesized and transsulfurated homocysteine. These findings demonstrated a possible interaction of different blood cells in the metabolism of methionine, as well as their potential role as a source of total plasma homocysteine in plasma.
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PMID:Synthesis and transsulfuration of homocysteine in blood. 813 55

Recent advances in determining anti-thrombogenic functions of vascular endothelial cells are reviewed. The following anticoagulant and fibrinolytic systems of endothelial cells are physiologically important; (1) Endothelial cell-derived metabolites including prostacyclin and nitric oxide (NO) support platelet inactivity. (2) Antithrombin III and tissue factor pathway inhibitor (TFPI) bound to heparin-like proteoglycans on endothelial cell membrane inhibit activated serine protease coagulation factors such as thrombin, factor Xa and factor VIIa-tissue factor complex. (3) Thrombomodulin converts thrombin from procoagulant into anticoagulant. Thrombin associated to thrombomodulin on endothelial cells activates protein C. Activated protein C in concert with protein S bound to endothelial cell membrane inactivates factors Va and VIIIa. (4) A receptor for both tissue plasminogen activator and plasminogen on endothelial cells provides an efficient plasmin generating system. Perturbation of these anti-thrombogenic systems of endothelial cells is caused by endotoxin (LPS), cytokines such as interleukin-1 and tumor necrosis factor (TNF), and risk factors for atherogenesis including lipoprotein(a) and homocysteine may result in arterial or venous thrombosis with subsequent development of atherosclerosis.
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PMID:[Anticoagulant and fibrinolytic systems of the injured vascular endothelial cells]. 817 40


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