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) is a sulfur-containing amino acid produced when methionine is demethylated. The majority of Hcy undergoes transsulfuration to cysteine by cystathionine beta-synthase (CBS), of which vitamin B6 (pyridoxine) is an essential cofactor. The remainder of Hcy is remethylated by methionine synthase (MS), of which vitamin B12 (cobalamin) is an essential cofactor along with methylenetetrahydrofolate (MTHF). MTHF is generated by the enzyme MTHFR-reductase (MTHFR). High levels of Hcy can result from a variety of aquired factors (deficiency of vitamins B6, B12 and folic acid, high meat diet, smoking and others) or genetic (abnormalities of methionine--homocysteine metabolism). Hyperhomocysteinemia is associated with premature atherosclerosis and venous thromboembolism; so called "cholesterol of XXI. age". Results of many studies suggest that hyperhomocysteinemia, homozygous state for MTHFR gene mutation, folate deficiency are probably risk factors for recurrent fetal loss, intrauterine fetal death, thrombo-embolic disease in pregnancy, neural tube defects and congenital cardiac malformation at infants and other placental diseases (pre-eclampsia, placental abruption and intrauterine growth restriction IUGR). Those irregularities are very interesting and important for obstetricians and gynecologists. The plasma homocysteine values can be modulated by vitamins, vitamin B6 and folic acid in particular. The potential for research and possible prevention in this area is immense.
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PMID:[Hyperhomocysteinemia and pregnancy complications]. 1518 72

Hyperhomocysteinemia is an important risk factor for atherosclerosis and it has recently been suggested as a diagnostic marker for Alzheimer disease (AD). The present studies compared homocysteinemia in patients with AD and with vascular dementia (VD),as well as in controls. Homocysteinemia was measured in 137 probable AD patients,diagnosed by the NINCDS-ADRDA criteria, in 40 probably VD patients diagnosed by the NINDS-AIREN criteria, and in 42 control subjects. Homocysteine levels were significantly higher in AD and VD groups, than in controls, however, VD patients were significantly older than the controls. The proportion of females was higher in the AD group, while serum folate and B12 vitamin levels tended to be lower in both the AD and VD groups, compared to the controls. In order to adjust the results for these potentially interfering factors, a multivariate ANCOVA calculation was performed, where homocysteine levels were analyzed considering 2 grouping factors (gender and neurological type) and 4 covariates (age, albumin,serum folate and vitamin B12 ). This analysis confirmed that even after adjusting for the covariates, the difference between AD and VD groups and controls remain highly significant,while neither the gender itself, nor the interaction of gender and the neurological type had any significant influence on the homocysteine levels. The main finding, therefore, is a significant increase of homocysteine levels in the 2 disease groups, compared to controls.
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PMID:Homocysteine in Alzheimer disease and vascular dementia. 1520 14

Homocysteine has been proposed as a risk factor for atherosclerotic disease and recurrent coronary stenosis due to neointimal hyperplasia following angioplasty. In order to evaluate homocysteine's role in human carotid neointimal hyperplasia, we have compared homocysteine levels in patients who have not developed restenosis with those who have within 2 years of carotid endarterectomy (CEA). One hundred and fifty-four patients were divided into 3 groups based on duplex scans performed 2 years after CEA. Group I (88) were patients in whom all scans showed no evidence of restenosis. Group II (35) patients exhibited some restenosis, but this did not exceed 49% diameter reduction based on our duplex criteria. Group III (31) patients developed a restenosis of > 50% within 2 years. One hundred and thirteen Dacron patches (73 Group I [83%], 22 Group II [63%], and 18 Group III [58%]) were used according to surgeon preference but did not affect the statistical relevance of homocysteine evaluation. The groups were otherwise identical in terms of age, sex, smoking history, and cholesterol levels. All patients were receiving antiplatelet medication postoperatively, and none had consumed added pharmacologic folate. The average homocysteine value for the entire study group was elevated at 12.5 micromol/L. The homocysteine values for the 3 groups were not statistically different (p > 1): (I, 12.5; II, 12.2; and III, 12.9 micromol/L). Elevated homocysteine levels (> 10 micromol/L) appear to be associated with carotid atherosclerosis, but at levels < 30 micromol/L do not appear to play a role in restenosis following CEA.
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PMID:Homocysteine, a risk factor for carotid atherosclerosis, is not a risk factor for early recurrent carotid stenosis following carotid endarterectomy. 1530 52

Homocysteine is an intermediate product in the methionine metabolism, which is catalysed by several enzymes with B2, B6, B12 vitamins and folic acid as cofactors. Moderate hyperhomocysteinemia, defined as total homocysteine concentration between 12 to 30 micromol/l, represents an independent risk factor for heart disease, vascular brain disease, phlebothrombosis and thromboembolic complications. It is related to placental abruptions, spina bifida and some neuropsychiatric disorders. Hyperhomocysteinemia is a metabolic syndrome based on interaction between genetic factors (most frequently 677C/T polymorphism of methylentetrahydrofolate reductase), diseases and demographic factors (smoking, aging, hormonal and nutritional factors). Moderate hyperhomocysteinemia occurs in about 20 to 30% of patients with clinical complications of atherosclerosis. Prospective and genetic studies have shown, that moderate hyperhomocysteinemia in healthy persons is only a weak predictor of cardiovascular diseases. Contrary to it, in patients with ischaemic heart disease, renal failure or diabetes mellitus and in thromboembolic disease, hyperhomocysteinemia represents a strong predictor of vascular morbidity and mortality. Toxic effects of hyperhomocysteinemia on the vascular wall can be explained by a chemical modification of lipoproteins and vascular structure, oxidative stress, endothelial dysfunction, inadequate endothelial cell regeneration, smooth muscle cell proliferation or by an accumulation of functionally non sufficient connective tissue. Also thrombogenic effects or an increased expression of cholesterol level controlling proteins and fatty acids in the liver can be considered. Treatment of hyperhomocysteinemia is based on the administration of pharmacological doses of folic acid, B6 and B12 vitamins, which can decrease total homocysteine concentration by 25 to 30%. Such decrease, which is in average 3 micromol/l, results in the decrease of relative risk of ischaemic heart disease by 11 to 16%, phlebothrombose by 25% and vascular brain diseases by 19 to 24%.
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PMID:[Consequences of moderate hyperhomocysteinemia in internal medicine]. 1530 62

Homocysteine has been recognized as a risk factor for atherosclerosis and arterial and venous thrombosis. Heart transplant patients have an increased prevalence of hyperhomocysteinemia. High homocysteine levels in transplant patients may promote development of cardiac allograft vasculopathy, but there is minimal information regarding the risk of venous thrombosis. The current case report illustrates the association of increased levels of homocysteine and hypercoagulable syndrome in a 36-year-old heart transplant patient with no previous history of clotting disorder. Both elevated homocysteine levels and extensive venous thrombosis responded promptly to treatment with a folate/B12/B6 vitamin combination and enoxaparin.
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PMID:Hyperhomocysteinemia and deep vein thrombosis in orthotopic heart transplantation: a case report. 1538 1

Homocysteine (Hcy) is a by-product of methionine metabolism. An imbalance of Hcy in the body may lead to hyperhomocysteinemia, a condition with elevated Hcy concentration in blood that may be one of the risk factors responsible for the development of several vascular diseases (thromboembolism, atherosclerosis, stroke, vascular diseases and dementia). Radix Salvia miltiorrhiza (Danshen), a well-known Chinese medicinal herb that can activate and improve blood microcirculation, is noticeable for its beneficial effect in treating cardiovascular diseases. The present study is to demonstrate the protective effect of Danshen extract against the homocysteine-induced adverse effect on human umbilical vein endothelial cell (HUVEC). Homocysteine (5 mM) not only decreased the cell viability but also caused the disruption of capillary-like structure formation in vitro. The protective effect of Danshen aqueous extract and its active compounds on endothelial cell function were demonstrated through an in vitro tube formation assay, which mimics the new blood vessel formation. To identify the active components in the aqueous extract of Danshen, the content was characterized by instrumental analysis using high performance liquid chromatography with diode array detector (DAD) and electrospray tandem mass spectrometry (ESI-MS/MS). Interestingly, Danshen extract and its pure compounds showed different effectiveness in protecting HUVEC against Hcy-induced injury according to the following descending order: Danshen aqueous extract, 3-(3,4-dihydroxy-phenyl)-2-hydroxy-propionic acid (Danshensu), protocatechuic acid, catechin and protocatechualdehyde. We believed that such findings might provide evidence in understanding the beneficial effects of Danshen on the cardiovascular system.
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PMID:Protective effects of Danshensu from the aqueous extract of Salvia miltiorrhiza (Danshen) against homocysteine-induced endothelial dysfunction. 1548 95

The causal relation of total Homocysteine (tHcy) to coronary heart diseases (CHD) is unclear. In vitro studies suggest a proinflammatory effect. Among 32,826 women from the Nurses' Health Study who provided blood samples in 1989-1990, 237 CHD events were documented during 8 years of follow-up. The cases (1:2) were matched to controls on age, smoking, and month of blood draw. Plasma tHcy was inversely associated with blood levels of folate (partial r = -0.3, P < 0.0001) and B1(2) (r = -0.2, P < 0.0001) and with dietary intake of folate (r = -0.1, P < 0.01) and B(2) vitamin (r = -0.1, P = 0.01). tHcy was positively associated with soluble tumor necrosis receptor (sTNF-R) 1 and 2 (partial r = 0.2, P < 0.0001). In a multivariate model adjusted for age, smoking, BMI, parental history, hypertension, diabetes, postmenopausal hormone use, physical activity and alcohol intake, the relative risk of CHD between the extreme quartiles of tHcy was 1.66 (95% CI; 1.05-2.64, P trend = 0.02). The association was not appreciably attenuated after further adjustments for sTNF-R1, sTNF-R2, CRP, or Total Cholesterol:/HDL-c ratio. tHcy is an independent risk predictor of CHD and modestly associated with TNF-receptors. However, the inflammatory biomarkers measured could not explain its role in CHD.
Atherosclerosis 2004 Dec
PMID:Homocysteine as a risk factor for coronary heart diseases and its association with inflammatory biomarkers, lipids and dietary factors. 1553 Sep 13

Homocysteine (H(e)) is an important and independent risk factor for atherosclerosis. We showed that human aortic smooth muscles in cultures proliferated significantly at a concentration of 25 micromol/L H(e) without the presence of serum. There was no effect of H(e) on apoptosis as determined by TUNEL-assay and gene expression of proapoptotic protein bax, caspases and TNFalpha families. However, collagen types I, III and IV increased significantly in a dose-dependent manner at elevated concentrations of H(e) and the amount of type VI collagen was significantly reduced in a dose-dependent manner. H(e) induced increased cell replication with an unaffected apoptosis rate. The present observations suggest that H(e) may contribute to accelerated progression of atherosclerotic lesions with collagen alterations which transform the injury into fibrotic plaques.
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PMID:Homocysteine and the production of collagens, proliferation and apoptosis in human arterial smooth muscle cells. 1560 9

Cardiovascular disease (CVD) is the principal cause of mortality in patients with chronic renal disease undergoing hemodialysis. In addition to the CVD risk factors, a new hypothesis has recently been aroused related to "new" factors involved in the development of atherosclerosis in the uremic patient; worthwhile mentioning are the homocysteine, inflammation, and oxidative stress, among others. The potential utility of the folic acid in the hyperhomocysteinemia control is well known, although its mechanism of action, either as antioxidant or anti-inflammatory, has not been established. Our results confirm that the patients undergoing dialysis demonstrate hyperhomocysteinemia, an increased inflammatory status, and an increase of the lipid peroxidation markers. The administration of IV folinic acid induces a reduction of homocysteine levels subordinate to the inflammatory status of the patient. Additionally, although no inflammatory effects were shown, the results provide evidence for the antioxidant effect of IV folinic acid administration by reducing the lipid peroxidation marker levels. The statistic analysis demonstrates no correlation among the 3 markers, in spite of its higher levels in these particular patients. Homocysteine does not independently predict mortality in patients taking oral folic acid. Nevertheless, the PCR (an inflammation marker) and the antibody antioxidative-LDL (a lipidic peroxidation marker) show a good prediction of mortality at the 24-month follow-up analysis. The knowledge of these "new" CV risk factors, as well as the factors that influence them, could be useful to prevent the development of atherosclerosis in patients with chronic renal disease.
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PMID:"New" cardiovascular risk factors in patients with chronic kidney disease: role of folic acid treatment. 1561 67

We investigated serum levels of lipids (total cholesterol, HDL-cholesterol, LDL-cholesterol, triglicerides), homocysteine, C-reactive protein (CRP) in 25 children with juvenile idiopathic arthritis (JIA) and 15 healthy control. We found statistically significant increase of total cholesterol, LDL-cholesterol, triglicerides (p<0.05) and decreased of HDL-cholesterol (p<0.05) in JIA patients compare to control group. Homocysteine correlated significantly with total cholesterol (r=0.47; p<0.05) and with LDL-cholesterol (r=0.53; p<0.05). In JIA children we found adverse lipids profile and increase of homocysteine level which may lead to early atherosclerosis.
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PMID:[Lipids and homocysteine level in juvenile idiopathic arthritis]. 1562 48


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