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

Moderate hyperhomocysteinaemia (MHH) is a risk factor for arteriosclerosis and thrombosis. About 10%-20% of the normal population have homocysteine levels contributing to an increased risk for arterial and venous disease. Main regulating enzymes of homocysteine metabolism are cystathionine beta-synthase (CBS) and methylenetetrahydrofolate reductase (MTHFR). Heterozygosity for CBS deficiency is most likely not an important cause for MHH in vascular disease. A recently discovered cause of MHH is reduced MTHFR activity due to a homozygous C677T mutation in the coding region of MTHFR. This mutation has been related to an increased risk for cardiovascular disease, although a number of studies are not confirmative. The elevated homocysteine levels due to this mutation can be normalized by administration of vitamins involved in homocysteine metabolism, in particular folate.
 ...
PMID:Mutated 5,10-methylenetetrahydrofolate reductase and moderate hyperhomocysteinaemia. 958 41

This study examines the effect of cysteine on the auto-oxidation of homocysteine, a process that has been implicated in the pathologic mechanism of hyperhomocystinemia with respect to arteriosclerosis and vascular disease. It is shown that homocysteine autoxidizes at a much slower rate than cysteine, but that low concentrations of cysteine or cystine dramatically accelerate homocysteine oxidation and increase the rate of homocysteine-dependent oxygen consumption. It is proposed that the major role of homocysteine is to reduce cystine to cysteine, and that cysteine autoxidation is the mechanism by which thiol-dependent oxidative stress occurs.
 ...
PMID:The effect of cyst(e)ine on the auto-oxidation of homocysteine. 1044 16

Increased levels of the physiological amino acid homocysteine (Hcy) are considered a risk factor for vascular disease. Hyperhomocysteinemia causes an intense remodelling of the extracellular matrix in arterial walls, particularly an elastolysis involving metalloproteinases. We investigated the activation of the latent elastolytic metalloproteinase proMMP-2 (72 kDa) by Hcy. Hcy was proved to exert a dual effect, activating proMMP-2 at low molar ratio (MR 10:1) and inhibiting active MMP2 at high molar ratio (MR > 1000:1). Methionine and the disulphide homocystine did not activate nor inhibit MMP-2, showing that the activation as well as the inhibition requires the thiol group to be free. The activation of proMMP-2 by Hcy is in accordance with the "cysteine-switch" mechanism, but occurs without further autoproteolysis of the enzyme molecule. In contrast with Hcy, the other physiological thiol compounds cysteine and reduced glutathione did not activate proMMP-2. These results suggest that the direct activation of proMMP2 by Hcy could be one of the mechanisms involved in the extracellular matrix deterioration in hyperhomocysteinemia-associated arteriosclerosis.
 ...
PMID:Influence of homocysteine on matrix metalloproteinase-2: activation and activity. 1049 21

Low-risk essential thrombocythemia patients include patients aged 18 to < 80 years with no vascular risk factor or previous thrombosis, no associated disease, a normal life expectancy, and a platelet count between 400 and 1,000 x 10(9)/L up to 1,500 x 10(9)/L. Asymptomatic essential thrombocythemia patients may be at risk for microvascular circulation disturbances. The indication for low-dose aspirin in asymptomatic essential thrombocythemia patients is uncertain, therefore randomization for aspirin 50 mg versus placebo is recommended. Symptomatic essential thrombocythemia patients with erythromelalgia and its ischemic complications, atypical transient ischemic attacks, minor stroke, visual disturbances and "superficial thrombophlebitis" in the absence of bleeding, vascular risk factors, or vascular disease have a clear indication for aspirin in a regular dose. To determine whether 50 mg/day is as effective as 100 mg/day for the prophylaxis of microvascular circulation disturbances in essential thrombocythemia, a randomized trial comparing low-dose aspirin 50 mg versus 100 mg at platelet counts between 400 and 1,000 up to 1,500 x 10(9)/L is recommended. To address the question whether reduction of the platelet count to normal (< 350 x 10(9)/L) is as effective as low-dose aspirin for the long-term relief of microvascular circulation disturbances, a randomized study comparing low-dose aspirin with the correction of platelet count to normal by anagrelide is recommended. High-risk essential thrombocythemia patients have a clear indication for platelet reductive therapy, including: (a) platelets > 1,500 x 10(9)/L, history of major thrombosis (myocardial infarction, stroke, peripheral occlusive vascular disease), or presence of vascular disease (e.g., arteriosclerosis); (b) history or presence of spontaneous or major bleedings, bleedings elicited by low-dose aspirin for the secondary prevention of vascular complications in essential thrombocythemia at platelet counts < 1500 x 10(9)/L, and side effects of long-term aspirin treatment such as gastritis; and progression from low- to high-risk essential thrombocythemia patients during follow-up or progressive myeloproliferative disease such as significant splenomegaly, myelofibrosis, leukocytosis, etc. To address the question of optimal treatment of high-risk essential thrombocythemia patients, randomization for anagrelide versus interferon at < 65 years of age and anagrelide versus hydroxyurea at an age > 65 years is recommended.
 ...
PMID:Aspirin and platelet-lowering agents for the prevention of vascular complications in essential thrombocythemia. 1072 22

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.
 ...
PMID:The C677T methylenetetrahydrofolate reductase gene mutation in hemodialysis patients. 1077 Sep 66

Recent epidemiological studies have shown that vascular risk factors may be involved in Alzheimer's disease (AD) as well as dementia in general. To investigate the relation between a vascular disorder and AD pathology, current criteria are defective because most depend on exclusion of a cerebrovascular disorder. Epidemiological studies have indicated the possibilities that arteriosclerosis, abnormal blood pressure, diabetes mellitus and smoking may be related to the pathogenesis of AD. As for the mechanism that vascular disorders influence AD, it is presumed that amyloid deposition may be caused by a vascular disorder. Alternatively, a vascular event may cause progression of subclinical AD to a clinical stage. Insulin resistance and apolipoprotein E may also be involved in these mechanisms. Our studies show that ischemia-induced the Alzheimer-associated gene presenilin 1 (PS1) and endoplasmic reticulum-stress, generated from a vascular disorder, may unmask clinical AD symptoms caused by presenilin mutation, suggesting that a vascular factor might be involved in the onset of familial AD.
 ...
PMID:Are cerebrovascular factors involved in Alzheimer's disease? 1086 6

Elderly diabetic patients were followed up prospectively for 4 years to see the effects of blood pressure and dyslipidemia on the development of diabetic micro- and macroangiopathies. We studied 84 elderly diabetic patients whom we divided into four groups according to the association of above complications: (1) diabetes alone group (DM), (2) hypertensive diabetic group (DM + HT), (3) hyperlipidemic diabetic group (DM + HL), and (4) hypertensive and hyperlipidemic diabetic group (DM + HTL). The treatment of diabetes was different among the groups. Glycemic control such as fasting blood glucose and HbA1c did not change between groups or through the follow-up years. As a matter of course, blood pressure of DM was lower and triglyceride of HTL was higher than in other groups. Microangiopathies such as retinopathy, nephropathy, and neuropathy and macroangiopathies such as ischemic heart disease (IHD), cerebral vascular disease (CVD), and arteriosclerosis obliterans were evaluated by using a grading scale according to the severity. The grade of microangiopathies in DM + HT increased gradually during the follow-up years and the grade of IHD and CVD in DM + HTL was relatively higher than in the other groups. Our findings support the general principle of control of hypertension and hyperlipidemia for the prevention of diabetic microangiopathy and macroangiopathy in the elderly diabetic patients.
 ...
PMID:Follow-up of elderly diabetics with or without hypertension and hyperlipidemia. 1090 22

Elevated homocysteine levels have been associated with arteriosclerosis and thrombosis. Hyperhomocysteinemia is caused by altered functioning of enzymes of its metabolism due to either inherited or acquired factors. Betaine-homocysteine methyltransferase (BHMT) serves, next to methionine synthase, as a facilitator of methyl group donation for remethylation of homocysteine into methionine, and reduced functioning of BHMT could theoretically result in elevated homocysteine levels. Recently, the genomic sequence of the BHMT gene was published. Mutation analysis may reveal mutations of the BHMT gene that could lead to hyperhomocysteinemia. In the present study we performed genomic sequencing of the BHMT gene of 16 vascular patients with hyperhomocysteinemia and detected three mutations in the coding region of this gene. The first was an amino acid substitution of glycine to serine (G199S), which was found only in the heterozygous state. The second mutation was a substitution of glutamine to arginine (Q239R), and the last mutation was an amino acid substitution of glutamine to histidine (Q406H). The latter was also found only in the heterozygous state. The relevance of these mutations was tested in a study group, which consists of 190 cases with vascular disease and 601 controls. The influence of these three mutations on homocysteine levels was investigated. None of the three mutations led to significantly changed homocysteine levels. In addition, no differences in genotype distribution between cases and controls were found. So far, our results provide no evidence for a role of defective BHMT functioning in hyperhomocysteinemia or subsequently in vascular disease.
 ...
PMID:Betaine-homocysteine methyltransferase (BHMT): genomic sequencing and relevance to hyperhomocysteinemia and vascular disease in humans. 1107 19

A variety of pathophysiological situations that affect cells of the vasculature, including endothelial and smooth muscle cells, leads to the expression of genes such as adhesion molecules and chemokines that are dependent on members of the nuclear factor (NF)-kappaB family of transcription factors. The corresponding gene products mediate important biological functions such as immune and inflammatory reactions, smooth muscle cell proliferation, and angiogenesis. The beneficial and usually transient NF-kappaB-dependent gene expression may be exaggerated in pathological situations and results in damage to the vessel wall and impaired vascular cell function. In this review, we will capitalize on the favorable and adverse roles of NF-kappaB in the context of vascular disease, eg, chronic and localized inflammation, arteriosclerosis, and neoangiogenesis.
 ...
PMID:The transcription factor NF-kappa B and the regulation of vascular cell function. 1107 59

Chronic exposure to arsenite is associated with vascular disease, such as arteriosclerosis. However, the cellular mechanisms for vascular disease in response to arsenic are not well known. The present study has demonstrated that arsenite not arsenate decreased the Fas ligand (FasL) expression on ECV304 cells through reactive oxygen species. Incubation of ECV304 cells with arsenite decreased the FasL expression and increased the intracellular peroxide levels. In addition, hydrogen peroxide was found to suppress FasL expression in a dose-dependent manner. The antioxidant, N-acetyl-cysteine, blocked the suppression of FasL expression in response to arsenite. These data suggested that arsenite initiates endothelium dysfunction, at least partly, by suppressing the FasL expression through activating reactive oxygen species sensitive endothelial cell signaling.
 ...
PMID:Suppression of Fas ligand expression on endothelial cells by arsenite through reactive oxygen species. 1151 1


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>