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)

Regulation of iron balance is of particular interest, especially iron absorption, cellular iron metabolism and transferrin-transferrin receptor in hematopoiesis. Recent advances in molecular and cell biology have helped to reveal the mysteries of cellular iron metabolism concerning mRNA encoding ferritin and transferrin receptor synthesis. The physiology of transferrin and transferrin receptor is applied in the evaluation of erythropoiesis, i.e., erythron transferrin uptake in ferrokinetics and measurement of serum transferrin receptor. In iron absorption, much of the key mechanism remains unknown. The importance of iron metabolism in human beings is discussed in traditional areas of iron deficiency and nutrition. Iron overload is a new clinical problem to be solved in hemochromatosis or in relation to ischemic heart disease.
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PMID:Overview of iron metabolism. 858 65

Iron deficiency severe enough to cause anemia is associated with significant morbidity while uncontrolled iron absorption which occurs in disorders such as hereditary hemochromatosis causes multiorgan failure and early death. Preliminary data from the Third National Health and Nutrition Examination Survey demonstrate that the prevalence of iron deficiency anemia in the United States is now very low. This implies that the current iron consumption is adequate for most individuals. An important unresolved question relates to the necessity for further reducing the prevalence of iron deficiency without anemia. More information is required to determine whether this lesser degree of iron deficiency is harmful. Recent survey data indicate that concomitantly with the reduced prevalence of iron deficiency there has been a rise in serum ferritin concentrations in American men and postmenopausal women. These findings have led to concern about the effectiveness of the physiological mechanisms for limiting storage accumulation in normal individuals and carriers of the hemochromatosis gene when dietary iron content is high. Furthermore, recent epidemiological observations suggest that a modest increase in iron stores (in a range previously considered safe) is a possible risk factor for ischemic heart disease and cancer; however, a causal relationship remains to be proven. Nonetheless, because there is no known benefit of high iron storage status, it seems prudent to avoid further increases in and possibly to reduce the dietary iron intake of men and postmenopausal women. Mean intake in these groups exceeds the current RDA by a significant margin. Therefore, the sources of dietary iron as well as other factors contributing to high serum ferritin values have to be defined. Also, efforts should be made to increase the awareness of professionals and the public about the possible risks of excessive dietary iron. The complexity of the Western diet and an incomplete understanding of all of the factors affecting serum ferritin concentrations make it very difficult to specify a safe upper range for daily iron intake at the present time.
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PMID:Deliberations and evaluations of the approaches, endpoints and paradigms for iron dietary recommendations. 881 5

Background-Homozygosity for a relatively common Cys282Tyr mutation of the human hemochromatosis-associated (HFE) gene was recently found to account for most cases of hereditary hemochromatosis. Because excess iron has been postulated to enhance risk of vascular disease, we studied whether occurrence of this mutation was associated with increased risk of first acute myocardial infarction in healthy middle-aged men in a prospective cohort study. Methods and Results-Study subjects were the 1150 participants in the population-based Kuopio Ischemic Heart Disease Risk Factor Study (KIHD), aged 42, 48, 54, or 60 years at baseline, who had no coronary heart disease at baseline and for whom a DNA sample was available. Information about myocardial infarctions was collected prospectively by use of FINMONICA (FINnish MONItoring of trends and determinants in CArdiovascular disease study) and hospital data. Events were classified by MONICA (MONItoring of trends and determinants in CArdiovascular disease study) diagnostic criteria. The HFE Cys282Tyr mutation was assayed by a solid-phase minisequencing technique. One subject was homozygous and 76 individuals were heterozygous for the HFE Cys282Tyr mutation (6.7%). During a mean follow-up of 9 years, 8 (10.4%) of 77 carriers and 60 (5.6%) of 1073 noncarriers experienced an acute myocardial infarction. In a Cox proportional hazards model allowing for the other strongest risk factors, the carriers had a 2.3-fold (95% CI 1. 1 to 4.8; P=0.03) risk of acute myocardial infarction compared with noncarriers. Conclusions-Male carriers of the common hemochromatosis gene mutation are at 2-fold risk for first acute myocardial infarction compared with noncarriers.
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PMID:Increased risk of acute myocardial infarction in carriers of the hemochromatosis gene Cys282Tyr mutation : a prospective cohort study in men in eastern Finland. 1049 67

Iron depletion was suggested to be protective against the development of ischemic heart disease. Population studies have led to conflicting results, and such an association has not been addressed in patients with heart failure due to cardiomyopathy. We studied the distribution of hemochromatosis-related mutations in 319 patients with heart failure due to cardiomyopathy of different etiologies. The genotypic distribution showed a significantly higher prevalence of heterozygotes for the C282Y mutation in patients with ischemic cardiomyopathy than in patients with cardiomyopathy of nonischemic etiologies (p = 0.0036). The frequency of the D63 mutation was not significantly different between ischemic versus nonischemic groups. In multiple logistic regression models adjusted for age, sex, ethnicity, and different degrees of disease progression, there was a strong and significant association of the C282Y mutation with ischemic cardiomyopathy compared with the nonischemic group (odds ratio 6.64, 95% confidence interval 1.71 to 25.73, after adjustment). In our sample, genetic variation in the HFE gene was associated with ischemic cardiomyopathy. Such association merits further study regarding its value as a prognostic marker in patients with ischemic heart disease.
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PMID:Hemochromatosis gene variants in patients with cardiomyopathy. 1154 59

Excessive body iron or iron overload occurs under conditions such as primary (hereditary) hemochromatosis and secondary iron overload (hemosiderosis), which are reaching epidemic levels worldwide. Primary hemochromatosis is the most common genetic disorder with an allele frequency greater than 10% in individuals of European ancestry, while hemosiderosis is less common but associated with a much higher morbidity and mortality. Iron overload leads to iron deposition in many tissues especially the liver, brain, heart and endocrine tissues. Elevated cardiac iron leads to diastolic dysfunction, arrhythmias and dilated cardiomyopathy, and is the primary determinant of survival in patients with secondary iron overload as well as a leading cause of morbidity and mortality in primary hemochromatosis patients. In addition, iron-induced cardiac injury plays a role in acute iron toxicosis (iron poisoning), myocardial ischemia-reperfusion injury, Friedreich ataxia and neurodegenerative diseases. Patients with iron overload also routinely suffer from a range of endocrinopathies, including diabetes mellitus and anterior pituitary dysfunction. Despite clear connections between elevated iron and clinical disease, iron transport remains poorly understood. While low-capacity divalent metal and transferrin-bound transporters are critical under normal physiological conditions, L-type Ca2+ channels (LTCC) are high-capacity pathways of ferrous iron (Fe2+) uptake into cardiomyocytes especially under iron overload conditions. Fe2+ uptake through L-type Ca2+ channels may also be crucial in other excitable cells such as pancreatic beta cells, anterior pituitary cells and neurons. Consequently, LTCC blockers represent a potential new therapy to reduce the toxic effects of excess iron.
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PMID:Role of L-type Ca2+ channels in iron transport and iron-overload cardiomyopathy. 1660 32

More than 25 years ago, the iron hypothesis proposed that a state of sustained iron depletion or mild iron deficiency exerts a primary protective action against ischemic heart disease. Iron depletion leads to a decreased availability of redox-active iron in vivo. The amount of free iron available at sites of oxidative or inflammatory injury appears to be a function of the stored iron level. Depletion of iron levels by phlebotomy, systemic iron chelation treatment or dietary iron restriction reduce atherosclerotic lesion size and increase plaque stability. In homozygous hemochromatosis there is commonly a defect that inhibits iron retention in macrophages. This defect may explain why atherosclerotic lesions appear to be less prevalent in this disorder. Findings of the "FeAST" trial have been recently reported. The trial assessed the potential benefit of mild iron reduction therapy in secondary prevention of cardiovascular disease. It was therefore not a fully valid test of primary prevention as postulated by the iron hypothesis. However, although no overall statistically significant cardiovascular benefit was found, in the youngest quartile at entry there were highly significant reductions in all cause mortality and in combined death plus non-fatal myocardial infarction and stroke in association with iron reduction therapy. The FeAST trial adds urgency to the initiation of new studies to assess the impact of maintenance of complete iron depletion in the primary prevention of cardiovascular diseases.
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PMID:[Current status of the iron hypothesis of cardiovascular diseases]. 1768 84