Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hemochromatosis is characterized by an excessive iron deposit in different tissues. Cardiac involvement may be observed in one third of the patients due to hemochromatosis and occurs as a consequence of ferritin accumulation in the heart which on one hand induces alterations in systolic and diastolic ventricular function and on the other hand, an arrythmogenic substrate. The clinical manifestations can be indistinctly related to atrial tachyarrhythmia, ventricular tachyarrhythmia, atrio-ventricular blockade and congestive heart failure, with the first being the most frequent. We present the case of one patient with secondary hemochromatosis to repeated transfusions due to sideroblastic anemia with cardiac involvement, whose initial heart manifestations were recurrent atrial tachyarrhythmia and sustained ventricular tachycardia with syncope for which an automatic defibrillator was implanted.
Rev Esp Cardiol 2001 Nov
PMID:[Ventricular tachycardia and cardiac hemochromatosis]. 1170 44

C-reactive protein (CRP) and lipids (e.g., low-density lipoprotein [LDL]) are both markers of cardiovascular disease risk, yet they are not highly correlated. Oxidative stress of lipids induced by iron may play a role in vascular inflammation, as indicated by CRP. The purpose of this study was to examine, in a representative sample of United States adults, the relation between ferritin, lipids, and CRP. We analyzed data on adults (aged > or =25 years) in the National Health and Nutrition Examination Survey III, a national public-use data set collected between 1988 and 1994. Ferritin, total cholesterol, LDL, high-density lipoprotein, and ferritin-lipid combinations were analyzed in relation to CRP in age-, gender-, and race-adjusted models as well as models with other potential confounding variables. In adjusted models, neither elevated ferritin (odds ratio [OR] 1.11, 95% confidence interval [CI] 0.94 to 1.32) nor elevated LDL was significantly associated with elevated CRP (OR 1.03, 95% CI 0.79 to 1.33). Patients with elevated ferritin and elevated LDL were more likely to have elevated CRP (OR 1.68; 95% CI 1.06 to 2.68). Patients with elevated ferritin and low high-density lipoprotein were also more likely to have elevated CRP (OR 1.71; 95% CI 1.28 to 2.27). These results suggest that both iron and lipids induce inflammation. Future research needs to focus on preventive medicine to decrease iron in patients with elevated lipids.
Am J Cardiol 2004 Mar 01
PMID:Association of ferritin and lipids with C-reactive protein. 1499 79

Heart failure secondary to iron overload is the main cause of death in patients with beta-thalassemia major. Combination therapy with deferoxamine and deferiprone has been shown to be more effective than either drug used alone in patients with beta-thalassemia major and symptomatic cardiomyopathy. Although monitoring the response to chelation therapy is usually carried out by indirect measurement of the serum ferritin level or by direct determination of tissue iron content in biopsy specimens, magnetic resonance imaging (MRI) seems to be useful for noninvasive qualitative and quantitative assessment of iron deposition. We present a case in which the efficacy of double chelation therapy in a patient with beta-thalassemia major and heart failure was demonstrated by MRI.
Rev Esp Cardiol 2006 Jan
PMID:[Magnetic resonance imaging evidence of the effectiveness of combination chelation therapy in iron overload cardiomyopathy]. 1643 9

Patients with hereditary hemochromatosis (HH) have been reported to develop diastolic functional abnormalities detectable by echocardiography, but it is unknown whether these occur in asymptomatic subjects. Thus, this study tested whether echocardiographic left ventricular (LV) relaxation abnormalities are detectable in subjects with asymptomatic HH. Forty-three asymptomatic subjects with HH (C282Y homozygosity in the HFE gene) and 21 age- and gender-matched control subjects without known HFE mutations underwent echocardiography with comprehensive diastolic functional evaluations. Subjects with HH were in New York Heart Association functional class I and consisted of 22 newly diagnosed patients (group A) and 21 chronically phlebotomized subjects with stable iron levels (group B). Group A subjects showed significant iron overload compared with group B subjects and controls (group C) (ferritin 1,164 +/- 886 [p <0.05 vs groups B and C], 128 +/- 262, and 98 +/- 76 microg/L and transferrin saturation 79 +/- 19% [p <0.05 vs groups B and C], 42 +/- 21%, and 26 +/- 10% for groups A, B, and C, respectively). Echocardiographic evaluation revealed (1) no statistically significant abnormalities of Doppler LV relaxation in HH groups; (2) significant augmentation of atrial contractile function in subjects with HH compared with controls, which was not correlated with iron levels and treatment status; and (3) the preservation of overall LV systolic function in HH groups. In conclusion, the results of this study suggest that the augmentation of atrial contraction appears to be an early detectable echocardiographic cardiac manifestation of abnormal diastolic function in asymptomatic subjects with HH, which may reflect undetectable subclinical LV relaxation abnormalities.
Am J Cardiol 2006 Oct 01
PMID:Significance of left atrial contractile function in asymptomatic subjects with hereditary hemochromatosis. 1699 82

Erythrocytosis is an adaptive response to improve oxygen transport in cyanotic congenital heart disease (CCHD). However, at highly increased hematocrit levels patients may experience hyperviscosity symptoms. Iron deficiency in CCHD patients is often overlooked due to elevated hemoglobin concentrations. A 29-year-old male with CCHD was readmitted to our outpatient clinic. Red blood cells (11.65*10(12)/L), hemoglobin (25.7 g/dL), and hematocrit (80%) were extremely elevated. Measurements of iron supply showed a constellation typical for iron deficiency with low ferritin (13.2 microg/L), and high sTfR (20 mg/L). We present a case of extremely high red blood cell counts with concomitant iron deficiency. For appropriate management and to avoid misinterpretation of the iron status, ferritin and sTfR should always accomplish laboratory examination of CCHD patients.
Int J Cardiol 2007 Mar 20
PMID:Iron deficiency in a patient with extreme erythrocytosis due to cyanotic congenital heart disease. 1709 63

Heart failure due to myocardial iron overload remains the leading cause of death in patients with transfusion-dependent anemias. Iron overload-induced cardiomyopathy is reversible if intensive chelation therapy is instituted on time. Thus, early detection of myocardial iron deposition is imperative to prevent overt heart failure. Conventional cardiac monitoring, including physical examination, electrocardiography, echocardiography or serum ferritin levels fail to predict manifest or subclinical myocardial involvement resulting from iron overload. Cardiovascular magnetic resonance imaging T2* (cMRI-T2*, pronounced T2 star) times correlate well with myocardial iron levels. This timely review focuses on the utility of cMRI-T2*, for the preclinical detection of myocardial iron overload and monitoring of myocardial iron content during chelation therapy.
Clin Cardiol 2009 Jun
PMID:Quantification of myocardial iron overload by cardiovascular magnetic resonance imaging T2* and review of the literature. 1841 44

Cardiovascular impairment is a major cause of morbidity and mortality in patients with thalassemia intermedia. In this study, echocardiographic assessment of left heart condition was performed in patients with thalassemia intermedia, and its relation to hematologic variables--amino terminal pro-brain natriuretic peptide (NT-proBNP), ferritin, hemoglobin--and liver iron concentration (LIC) was investigated. Echocardiographic assessment was performed using pulse-wave Doppler and tissue Doppler imaging. Data from 74 patients with thalassemia intermedia--35 men, 39 women, mean age 26.5 years (8 to 63)--were randomly selected and evaluated. Blood samples were collected for NT-proBNP levels in a random subgroup of 19 patients. Mean baseline values were hemoglobin 8.4 g/dl (4.9 to 13.1), serum ferritin 902.6 ng/ml (15 to 4,140), LIC 9.0 mg Fe/g (0.5 to 32.1), and NT-proBNP 113.5 pg/ml (16.4 to 371). Correlation between LIC and pulmonary artery systolic pressure was significant, suggesting that iron loading in the liver is indicative of cardiovascular sequelae. NT-proBNP was significantly correlated with the ratio of the left ventricular early rapid filling wave to early diastolic velocity at the mitral annulus (r = 0.50, p = 0.04) and hemoglobin (r = -0.49, p = 0.03), but not with other characteristics assessed. In conclusion, this study has highlighted the importance of using tissue Doppler imaging rather than pulse-wave Doppler to characterize left ventricular diastolic dysfunction in patients with thalassemia intermedia. Demonstration of the correlation of LIC and pulmonary artery systolic pressure independent of left ventricular filling pressures supports our hypothesis that left ventricular diastolic dysfunction does not contribute to the increased pulmonary artery systolic pressure in patients with thalassemia intermedia.
Am J Cardiol 2008 Aug 01
PMID:Relation between iron-overload indices, cardiac echo-Doppler, and biochemical markers in thalassemia intermedia. 1863 3

Thalassemia is a congenital hemoglobinopathy leading to anemia because of impaired erythropoiesis and peripheral hemolysis. Thalassemia major patients are transfusion dependent and it results in iron accumulation. The heart is one of the major organs affected with iron overload and iron induced cardiac dysfunction (pump and conduction abnormalities) remains the number one cause of death among thalassemia major patients. It has been reported that a high ferritin concentration is related to high troponin levels in hemodialysis patients receiving more intravenous iron sucrose. Abnormal troponin I levels have also been reported without acute coronary syndrome. We present a case of abnormal troponin I levels in Thalassemia major patient with high ferritin concentration, permanent atrial fibrillation and without acute coronary syndrome. To our knowledge, this is the first report of abnormal troponin I levels in a Thalassemia major patient with high ferritin concentration and without acute coronary syndrome and also this case focuses attention on the importance of the correct evaluation of abnormal troponin I levels.
Int J Cardiol 2010 Jan 21
PMID:Abnormal troponin I levels in a thalassemia major patient with high ferritin concentration, permanent atrial fibrillation and without acute coronary syndrome. 1868 84

Ischemic preconditioning is a well-known procedure transiently protecting the heart against injury associated with prolonged ischemia, through mechanism/s only partly understood. The aim of this study was to test whether preconditioning-induced protection of the heart involves an iron-based mechanism, including the generation of an iron signal followed by accumulation of ferritin. In isolated rat hearts perfused in the Langendorff configuration, we measured heart contractility, ferritin levels, ferritin-iron content, and mRNA levels of ferritin subunits. Ischemic preconditioning caused rapid accumulation of ferritin, reaching 359% of the baseline value (set at 100%). This was accompanied by a parallel decline in ferritin-bound iron: from 2191+/-548 down to 760+/-34 Fe atoms/ferritin molecule, p<0.05. Ferritin levels remained high during the subsequent period of prolonged ischemia, and returned to nearly the baseline value during the reperfusion phase. Selective iron chelators (acetyl hydroxamate or Zn-desferrioxamine) abrogated the functional protection and suppressed ferritin accumulation, thus demonstrating the essentiality of an iron signal in the preconditioning-induced protective mechanism. Moreover, introduction of an iron-containing ternary complex, known to import iron into cells, caused a three-fold accumulation of ferritin and simulated the preconditioning-induced functional protection against prolonged myocardial ischemia. The ischemic preconditioning-and-ischemia-induced increase in ferritin levels correlated well with the accumulation of ferritin L-subunit mRNA: 5.44+/-0.47 vs 1.23+/-0.15 (units) in the baseline, p<0.05, suggesting that transcriptional control of ferritin L-subunit synthesis had been activated. Ischemic preconditioning initiates de novo synthesis of ferritin in the heart; the extra ferritin is proposed to serve a 'sink' for redox-active iron, thus protecting the heart from iron-mediated oxidative damage associated with ischemia-reperfusion injury. The present results substantiate a novel iron-based mechanism of ischemic preconditioning and could pave the way for the development of new modalities of heart protection.
J Mol Cell Cardiol 2008 Dec
PMID:Heart protection by ischemic preconditioning: a novel pathway initiated by iron and mediated by ferritin. 1881 83

Ferritin heavy chain (FHC) protein was significantly reduced in murine failing hearts following left coronary ligation or thoracic transverse aortic constriction. The mRNA expression of FHC was not significantly altered in failing hearts, compared to that in control sham-operated hearts. Prussian blue staining revealed spotty iron depositions in myocardial infarct failing hearts. Oxidative stress was enhanced in the myocardial infarct failing hearts, as evidenced by increases in 4-hydroxy-2-nonenal and 8-hydroxy-2'-deoxyguanosine immunoreactivity. To clarify the functional significance of FHC downregulation in hearts, we infected rat neonatal cardiomyocytes with adenoviral vector expressing short hairpin RNA targeted to FHC (Ad-FHC-RNAi). The downregulation of FHC induced a reduction in the viability of cardiomyocytes. The relative number of iron deposition-, 4-hydroxy-2-nonenal- or 8-hydroxy-2'-deoxyguanosine-positive cardiomyocytes was significantly higher in Ad-FHC-RNAi-infected cardiomyocytes than in control vector-infected cardiomyocytes. Treatment of Ad-FHC-RNAi-infected cardiomyocytes with desferrioxamine, an iron chelator, significantly reduced the number of iron, 4-hydroxy-2-nonenal or 8-hydroxy-2'-deoxyguanosine-positive cells, and increased viability. In addition, treatment with N-acetyl cysteine, an antioxidant, significantly reduced the number of 4-hydroxy-2-nonenal- or 8-hydroxy-2'-deoxyguanosine-positive cells. Reduced viability in Ad-FHC-RNAi-infected cardiomyocytes was significantly improved with N-acetyl cysteine treatment. These findings indicate that excessive free iron and the resultant enhanced oxidative stress caused by downregulation of FHC lead to cardiomyocyte death. The decrease in FHC expression in failing hearts may play an important role in the pathogenesis of heart failure.
J Mol Cell Cardiol 2009 Jan
PMID:Downregulation of ferritin heavy chain increases labile iron pool, oxidative stress and cell death in cardiomyocytes. 1899 54


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