Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atherosclerosis with or without thrombosis superimposed is the most frequent cause of ischemic heart disease (IHD), peripheral arterial disease, and a main cause of stroke. Conflicting results have been reported in genetic, observational, and experimental studies on the relationship between homocysteine and these atherothrombotic diseases. Although cardiovascular complications are common in homocystinuric patients (severe hyperhomocysteinemia), IHD, the most frequent manifestation of atherothrombosis in the general population, appears to be rare. On the basis of findings in individuals with hyperhomocysteinemia of genetic origin, there is in fact no clear evidence for a causal role of homocysteine in the pathogenesis of atherothrombotic disease, and the positive association between plasma homocysteine and IHD observed in many, but not all epidemiologic studies does not prove causality. To infer causality from observational studies, there should be a temporal, consistent, strong, independent, graded (dose-response effect), and duration-dependent relationship between exposure and outcomes, and a biologically plausible mechanism should exist. The relationship between plasma homocysteine levels and IHD does not fulfill these criteria beyond reasonable doubt. In the general population, plasma homocysteine levels are to a great extent determined by dietary habits, and plasma homocysteine could be a marker, or a consequence, of atherothrombosis and/or risk-associated behavior (e.g., a diet low in fruits and vegetables) rather than a cause of atherothrombosis. Experimentally, hyperhomocysteinemia is not in itself atherogenic in normal animals with relatively low plasma cholesterol levels. The homocysteine theory of atherosclerosis should be tested more thoroughly in hypercholesterolemic animals that develop atherosclerosis spontaneously to determine whether elevated plasma homocysteine levels are harmful under atherogenic conditions. A causal role of homocysteine in atherothrombotic disease remains to be established.
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PMID:Homocysteine and atherothrombosis. 1183 89

Homocysteine is a significant but modifiable risk factor for vascular diseases. While several pathological processes may be involved, homocysteine can cause significant endothelial impairment and compromise vascular NO bioactivity. In the present study, we aimed to assess effects of homocysteine on NO-mediated hemodynamic responses in vivo. We created an acute hyperhomocysteinemia model (plasma homocysteine of 65-276 micromol/l) by continuous venous infusion of D,L-homocysteine to anaesthetized Sprague-Dawley rats. Vasodilators including NO donors: S-nitrosohomocysteine (SNOHcy), S-nitrosocysteine (SNOCys) and sodium nitroprusside (SNP), the endothelial NO synthase (eNOS) activator: acetylcholine (ACh), and calcium channel blocker: verapamil and nicardipine, were administered by one bolus injection to the homocysteinemic rats. While homocysteine infusion produced no change in the mean femoral arterial blood pressure, each of these vasodilators led to a rapid and substantial dose-dependent fall in blood pressure. Concurrent homocysteine infusion, however, attenuated the blood pressure lowering effects induced by NO donors (P<0.01), but not by the calcium channel blockers. Homocysteine inhibited not only the endothelial-derived NO as stimulated by ACh, but also the bioactivity of exogenously supplied NO by SNOHcy, SNOCys and SNP. Our findings indicate that homocysteine may have an effect on NO bioproduction and bioavailability. Vasodilating efficacy of commonly used NO donors such as nitroglycerine may be seriously compromised by hyperhomocysteinemia, which is common among ischemic heart disease patients.
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PMID:Homocysteine attenuates hemodynamic responses to nitric oxide in vivo. 1188 29

Hyperhomocysteinemia is known to be associated with many of the occlusive vascular diseases including ischemic heart disease. Elevated plasma total homocysteine (t-Hcy) is also remarkably common among patients with moderate to severe renal failure. The purpose of this study was to investigate the role of homocysteine (Hcy) in the pathogenesis of diabetic nephropathy in the rat. Additionally, any effect of aminoguanidine (AG), an inhibitor of advanced glycation end product (AGE) formation, on the onset of nephropathic symptoms and on the concentrations of Hcy was searched for. Diabetes was induced in male Wistar albino rats (6 months old) by a single injection of 50 mg x kg (-1)streptozotocin (STZ) into the penile vein. Animals with blood glucose levels higher than 350 mg x dl (-1)72 h after STZ injection were included in the study. Age-matched rats receiving a single dose of citrate buffer served as controls. One half of the control and diabetic groups received AG via drinking water (1 g l (-1)). The experimental period lasted for ten weeks. Animals were killed by cardiac venipuncture after 24 hour urine samples were collected. Serum t-Hcy was quantified using HPLC, and urinary GAGs using the spectrophotometric 1,9-dimethyl methylene blue dye method. Serum glucose, protein, creatinine and total sulfydryl (t-SH) measurements, and urinary protein determinations were carried out spectrophotometrically. In diabetic rats, serum t-Hcy levels were significantly decreased (P< 0.001), and were negatively correlated with the urinary protein concentration (r= -0.67, P< 0.05). Urinary GAG levels were also increased in diabetic rats (P< 0.001). AG neither affected the t-Hcy levels, nor ameliorated the nephropathic symptoms. These results indicate that diabetic nephropathy is not linked to homocysteinemia in the rat.
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PMID:A study on the relationship between homocysteine and diabetic nephropathy in rats. 1188 23

Hyperhomocysteinemia is recognised as a risk factor of ischaemic heart disease and vascular complications of arterial hypertension. Methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism is associated with hyperhomocysteinaemia. The aim of the study was the assessment of an association of the above polymorphism with type 2 diabetes with special attention to myocardial infarction and arterial hypertension accompanying diabetes. The study group consisted of 172 type 2 diabetics. 172 control subjects with normal glucose tolerance were age and sex matched to patients with diabetes. C677T polymorphism in MTHFR gene locus was detected using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method. CT and TT genotypes were found more often among diabetics (OR 1.83, 95% CI 1.16-2.89; p < 0.01). This finding may be secondary to the excess of T allele bearers among diabetics with myocardial infarction when compared to diabetics without infarction and to control group. Upon obtained results the potential role of genotypes CT and TT as risk factors of myocardial infarction among patients with type 2 diabetes could not be excluded (OR 2.33, 95% CI 0.93-5.8; p = 0.07). Genotypes containing T allele are not associated with diabetes type 2 and concomitant arterial hypertension (OR 1.45, 95% CI 0.89-2.57; p = 0.14). A confirmation in further studies is needed for the presented findings.
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PMID:[Methylenetetrahydrofolate reductase gene polymorphism in patients with type 2 diabetes]. 1192 64

Homocysteine induces endothelial injury and inhibits endothelial cell proliferation, which is a key role in angiogenesis. The purpose of this study was to investigate whether the plasma level of homocysteine is associated with the development of collaterals in patients with single-vessel coronary artery disease (CAD). Among a series of 105 male patients with angiographic estimation, 49 with single-vessel CAD were intensively investigated. Development of collaterals was classified by Rentrop's method. Univariate and multivariate analyses revealed that hyperhomocysteinemia negatively affected the development of collaterals (p=0.0015 and 0.0011, odds ratio 0.69, 95% confidence interval 0.52-0.90), whereas the duration of angina and percent stenosis evaluated by quantitative coronary angiography had a positive affect. Moreover, the level of homocysteine in the group with poorly developed collaterals (n=7, Rentrop class 0 and 1) was significantly higher than that in the group with well-developed collaterals (n=12, Rentrop class 2 and 3) of the patients with single-vessel disease showing total occlusion (p=0.034). This study clearly demonstrates that the plasma level of homocysteine is independently and inversely associated with the development of collateral circulation in CAD patients. Homocysteine might be a new undesirable aspect of ischemic heart disease through its inhibition of collateral development.
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PMID:Plasma level of homocysteine is inversely-associated with the development of collateral circulation in patients with single-vessel coronary artery disease. 1199 40

Hyperhomocysteinemia (HHcy) is a newly recognized risk factor for myocardial infarction, however, the effect of HHcy on endothelium-dependent flow-induced dilation of coronary arteries is not known. Thus, changes in diameter of small intramural coronary arteries (diameter, approximately 145 microm) isolated from control rats and rats with methionine diet-induced HHcy were investigated by videomicroscopy. Increases in intraluminal flow (from 0 to 40 microl/min) elicited dilations of control vessels (maximum, 25 +/- 2 microm), responses that were absent in HHcy arteries. The nitric oxide (NO) synthase inhibitor L-NAME inhibited flow-induced dilation of control coronaries, whereas it had no effect on responses of HHcy arteries. Dilations of control and HHcy arteries to the NO donor sodium nitroprusside were not different. Responses to flow in HHcy coronary arteries were unaffected by administration of L-arginine or the prostaglandin H(2)/thromboxane A(2) receptor antagonist SQ 29,548. However, in the presence of superoxide dismutase (plus catalase) or the superoxide scavenger Tiron increases in flow elicited L-NAME-sensitive dilations of HHcy coronaries (maximum, 18 +/- 5 microm). Also, superoxide dismutase significantly reduced the enhanced superoxide production of HHcy coronaries (measured by the lucigenin chemiluminescence method). Single vessel Western blotting showed an increased tyrosine nitrosation (a stable biomarker of tissue peroxynitrite formation) in HHcy coronaries. Also, extensive prevalence of 3-nitrotyrosine immunoreactivity was observed in HHcy coronaries that was confined primarily to the subendothelial layers of smooth muscle. We propose that in HHcy an increased level of superoxide scavenges NO forming peroxynitrite, which increases protein nitrosation. The reduced bioavailability of NO impairs flow-induced dilations of coronary arteries, which may contribute to the development of coronary atherosclerosis and ischemic heart disease.
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PMID:Impaired nitric oxide-mediated flow-induced coronary dilation in hyperhomocysteinemia: morphological and functional evidence for increased peroxynitrite formation. 1210 99

Hyperhomocysteinemia is currently regarded as a risk factor for the development of ischemic heart disease (IHD). We examined the relation between plasma total homocysteine (tHCY) concentrations and the severity and morphology of coronary stenosis in 238 Japanese patients. Coronary stenosis score (CS) in the first quartile of plasma tHCY levels was 4.9 and the second, third and fourth quartiles were 6.5, 7.5, and 8.9, respectively and plasma tHCY levels were 8.5, 10.9, 13.5, and 22.4 mumol/l, respectively. CS was higher in the fourth quartile than in the first, suggesting that plasma tHCY levels are related to the coronary stenosis severity. Among 238 patients, 123 did not have any significant coronary stenosis (group 1), 98 had focal coronary stenosis (group 2) and 17 had diffuse coronary stenosis (group 3). Plasma tHCY level was higher in group 3 than in group 1 or 2, suggesting that plasma tHCY levels are related to the diffuse coronary stenosis. We also examined whether hyperhomocysteinemia is concerned in coronary spasm. Plasma tHCY levels did not differ between 43 patients with vasospastic angina and 43 patients without ischemic heart disease, suggesting that plasma tHCY levels are not concerned in coronary spasm. Therefore, in Japanese patients, plasma tHCY contributes to the development of IHD through the influence on chronic coronary atherosclerotic background, but not through the influence on coronary spasm, i.e., one of the acute ischemic stimuli. Whether or not tHCY influences coronary thrombosis should be clarified in Japanese patients.
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PMID:[Homocysteine as a risk factor for ischemic heart disease]. 1237 18

Cardiovascular disease is the main cause of death in end-stage renal failure treated by hemodialysis or peritoneal dialysis. Though reduced in renal transplant recipients compared to the dialysis population, an excess cardiovascular mortality is still present after transplantation. The authors are reviewing the main data on mortality in the renal transplant population, focusing on major risk factors: ischaemic heart disease, hypercolesterolemia, smoking, hyperhomocysteinemia. The presence of these factors and the extent of cardiac and vascular abnormalities in the dialytic patient are closely related to outcomes in the post-transplant period. It is thus mandatory to approach and minimize all these in the dialytic and even predialytic period of chronic renal failure in order to reduce renal transplant mortality in patients with functioning grafts. Finally, an algorythm in managing cardiovascular disease pre- and post-transplantation is proposed.
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PMID:[Cardiovascular risk after renal transplantation(II): ischemic heart disease, hypercholesterolemia, hyperhomocysteinemia and smoking]. 1263 56

Hyperhomocysteinemia is widely recognised as an emerging risk factor of endothelial dysfunction and vascular damage. In this study we wanted to verify if it, when associated to arterial hypertension--traditional risk factor--represents a higher added risk of organ damage during menopause, which is a condition connected to a higher incidence of cerebrovascular diseases. A survey of 30 postmenopausal women with similar characteristics (BMI, age, absence of relevant pathologies such as diabetes, metabolic disorders and absence of smoking) was selected (menopause had occurred from 12 to 16 months at the moment of observation). At the moment of the observation they had not gone through any continuous pharmacological therapy. They were subdivided into 3 groups: normotensive; hypertensive (with 2nd degree hypertension: mild to moderate) without organ damage; hypertensive with organ damage (TIA, ischaemic heart disease, etc.). The carotid IMT, measured with ultrasound method, was considered as an organ damage parameter. 43% of the patients had high levels of homocysteine (> 15 micromol/l), which are levels considered at risk in other surveys. The highest levels of homocysteine were recorded in hypertensive women with episodes of acute cerebrovascular damage (micromol/l = 24.3 +/- 8.9). In this group, a positive correlation (r = 0.7) was obtained between homocysteine levels and carotid IMT. The possible coexistence of hyperhomocysteinemia and arterial hypertension, even though without particularly high values for both of them, in menopause may represent a dangerous association responsible for a significant organ damage and, therefore, for acute cerebrovascular events.
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PMID:Hyperhomocysteinemia in menopausal hypertension: an added risk factor and a dangerous association for organ damage. 1272 36

Although renal failure has classically been associated with a bleeding tendency, thrombotic events are common among patients with end-stage renal disease (ESRD). A variety of thrombosis-favoring hematologic alterations have been demonstrated in these patients. In addition, "nontraditional" risk factors for thrombosis, such as hyperhomocysteinemia, endothelial dysfunction, inflammation, and malnutrition, are present in a significant proportion of chronic dialysis patients. Hemodialysis (HD) vascular access thrombosis, ischemic heart disease, and renal allograft thrombosis are well-recognized complications in these patients. Deep venous thrombosis and pulmonary embolism are viewed as rare in chronic dialysis patients, but recent studies suggest that this perception should be reconsidered. Several ESRD treatment factors such as recombinant erythropoietin (EPO) administration, dialyzer bioincompatibility, and calcineurin inhibitor administration may have prothrombotic effects. In this article we review the pathogenesis and clinical manifestations of thrombosis in ESRD and evaluate the evidence that chronic renal failure or its management predisposes to thrombotic events.
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PMID:Thrombosis in end-stage renal disease. 1471 19


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