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)

We investigated the presence of low-molecular-weight iron and ferritin in human atheromas, and their possible relation to the apoptotic process. Arterial wall segments with fatty streaks were collected from coronary arteries and thoracic aortas of 12 clinical autopsy cases with general atherosclerosis. Normal appearing regions from the same cases together with normal coronary arteries from seven young forensic autopsy cases, without any sign of atherosclerosis, were used for comparison. Anti-CD68 (macrophage marker) and anti-ferritin antibodies were applied to serial sections of the arterial wall segments, fixed in formadehyde and embedded in paraffin wax, using an avidin-biotin complex (ABC) technique. Similarly, apoptotic cells were assayed by the TUNEL technique, while low-molecular-weight iron was cytochemically detected by autometallography. Cell counting and computerised image analysis were performed to compare the distribution of macrophages, ferritin- and iron-rich cells, and apoptotic cells in the intima, media, and adventitia of the arteries. Pronounced ferritin accumulation, occurrence of lysosomal low-molecular-weight iron, and apoptosis mainly concerned CD68-positive cells (macrophages) in the atherosclerotic lesions. No ferritin- or CD68-positivity was found in normal coronary arteries from the young forensic-autopsy cases, while a moderate number of such cells were observed in the intima of normal looking vessel areas from the control cases. In the intima, cytosolic ferritin and low-molecular-weight iron with a lysosomal type distribution were found in many CD68-positive macrophages which frequently were surrounded by erythrocytes. A substantial number of apoptotic cells within the intima, media, and adventitia were registered in all atherosclerotic lesions examined, although mainly in the vulnerable macrophage-enriched areas of the atheroma shoulder. We suggest that iron may occur within the cytosol, mainly bound in ferritin, but also in low-molecular weight, redox-active form within the acidic vacuolar apparatus of macrophages and macrophage-derived foam cells following erythrophagocytosis or phagocytosis of apoptotic cells. Low-molecular-weight iron within lysosomes, present due to degradation of iron-containing structures, such as ferritin, may partially become exocytosed and contribute to cell-mediated LDL-oxidation. Moreover, such lysosomal iron may also sensitise lysosomes to oxidative stress and induce apoptosis of macrophage/foam-cells that may result in instability and rupture of atherosclerotic plaques.
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PMID:Apoptotic macrophage-derived foam cells of human atheromas are rich in iron and ferritin, suggesting iron-catalysed reactions to be involved in apoptosis. 1071 92

Serum ferritin levels were determined in a group of 148 subjects drawn from a community study who were found to be at high risk of atherosclerosis (evaluated on the basis of the following data: levels of non-HDL cholesterol, arterial pressure, smoking status, cardiovascular or cerebrovascular disease in a subject's history, diabetes mellitus, a positive family predisposition to, or accumulation of the above factors) and compared with the levels obtained in a control group of 148 examined age- and sex-matched subjects from the same community with non-significant risk factors. Mean serum ferritin levels were higher in the whole risk group and in the subgroups of risk men and postmenopausal women than in the corresponding controls (the whole risk group: 263.4 +/- 218.5 micrograms/l vs. 198.3 +/- 179.5 micrograms/l, p < 0.05; the subgroup of men 361.8 +/- 235.7 micrograms/l vs. 286.4 +/- 194.6 micrograms/l, p < 0.05 and the subgroup of postmenopausal women 184.1 +/- 143.1 vs. 126.7 +/- 108.4 micrograms/l, p < 0.05).
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PMID:Serum ferritin levels in subjects at high risk of atherosclerosis. 1076 18

Aspirin reduces the incidence of thrombotic occlusive events. Classically this has been thought to be due to the platelet inhibitory action of aspirin but it has recently been shown that inflammation plays a predominant role in the initiation and progression of lesions in atherosclerosis. In humans, treatment with aspirin reduces cardiovascular risk and slows carotid plaque growth in a dose-dependent fashion. We have explored this issue in Apo E-deficient mice on a high-fat, high cholesterol diet which provided these animals with a continuous administration of 500 microg/day of acetylsalicylic acid in the drinking water. After 10 weeks of treatment, the size of the atherosclerotic lesion at the aortic sinus had reduced by 35%. At the end of the trial there were no significant changes in either plasma lipids or in the quantitative distribution among lipoproteins. Likewise, the total antioxidant status and the resistance of plasma to oxidation in vitro was similar and there was no change in the distribution of iron deposits and in the relative composition of plasma pro-oxidants and antioxidants, or in the concentration of plasma in ferritin. Therefore, it is our hypothesis that the antiinflammatory effect is responsible for the reduction in lesion size. We propose that antiinflammatory molecules which do not cause gastrointestinal complications should be tested in humans to determine long-term efficacy in the attenuation of atherosclerosis.
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PMID:The continuous administration of aspirin attenuates atherosclerosis in apolipoprotein E-deficient mice. 1120 94

Insulin resistance syndrome (IRS) is a cluster of prevalent conditions including glucose intolerance, hypertension and dyslipidemia, which commonly predispose to cardiovascular disease. However, the mechanism by which IRS is related with cardiovascular disease is not yet settled. Recently, it has been hypothesized that atherosclerosis is an inflammatory disease and that an increase in oxidative stress plays a key role in causing endothelial dysfunction associated with atherosclerosis. There has been, however, no study directly relating IRS with oxidative stress in human subjects. We measured various markers of oxidative stress among subjects who participated in a population-based epidemiological study performed in 1996. IRS was defined as non-diabetic subjects having more than two of three salient features of the syndrome (glucose intolerance, hypertriglyceridemia/low high density lipoprotein (HDL)-cholesterol and hypertension). The subjects with IRS (n=70) showed higher plasma malondialdehyde (MDA; 2.10+/-1.43 vs. 1.63+/-1.21 micromol/ml, P=0.009), homocysteine (16.32+/-8.34 vs. 13.06+/-6.49 micromol/l, P=0.002) and ceruloplasmin concentrations (29.80+/-5.28 vs. 27.39+/-5.10 mg/dl, P=0.002) than control subjects (n=196). Plasma MDA concentration was positively correlated with waist-to-hip ratio (r=0.124, P=0.044), and with plasma triglyceride (TG; r=0.163, P=0.008), ferritin (r=0.200, P=0.002) and homocysteine concentrations (r=0.136, P=0.032). These results suggest that increase in oxidative stress may contribute to the development of cardiovascular disease in IRS.
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PMID:Oxidative stress markers in Korean subjects with insulin resistance syndrome. 1173 6

We investigated intracellular oxidative modification of low density lipoprotein (IOM-LDL) by endothelial cells (ECs) and the role of ferritin in this process. IOM-LDL was examined by immunocytochemistry with an anti-oxidized phosphatidylcholine antibody and by lipid peroxidation assay. Incubation of LDL-treated ECs (human umbilical vein endothelial cells, passage 3) with ferritin produced cytoplasmic immunostain with the antibody, especially in large or giant ECs, and the formation of thiobarbituric acid-reactive substance (TBARS) in these cells. These observations suggest that ECs can perform IOM-LDL. Incubation with the iron chelator deferoxamine or pretreatment of LDL-treated ECs with deferoxamine suppressed ferritin-induced IOM-LDL by greater than 60%. Antioxidants dimethylsulphoxide and butylated hydroxytoluene markedly inhibited IOM-LDL, but mannitol did so only mildly. Catalase and superoxide dismutase had little or no effect on IOM-LDL. Apoferritin substituted for ferritin did not induce IOM-LDL. Our data suggest that IOM-LDL is mediated by intracellular hydroxyl radical formation, which is catalyzed mainly by free iron released from ferritin, and that ECs contribute to the development of atherosclerosis via IOM-LDL.
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PMID:Intracellular oxidative modification of low density lipoprotein by endothelial cells. 1195 23

Controversy surrounds the role of iron (Fe) in atherosclerosis (ASCVD), mainly due to the inaccuracy of assessing body Fe stores with serum ferritin and transferrin saturation. Quantitative phlebotomy was used to test whether or not (a) Fe stores are increased in individuals at high risk for ASCVD and (b) Fe depletion to near-deficiency (NID) levels is associated with reduction of risk factors for ASCVD. Thirty-one carbohydrate-intolerant subjects completed the study. Fe stores were within normal limits (1.5 +/- 0.1 g). At NID, a significant increase of HDL-cholesterol (p < 0.001) and reductions of blood pressure (p < 0.001), total and LDL-cholesterol (p < 0.001), triglyceride (p < 0.001), fibrinogen (p < 0.001) and glucose and insulin responses to oral glucose loading (p < 0.001) were noted, while homocysteine plasma concentration remained unchanged. These effects were largely reversed by a 6-month period of Fe repletion with reinstitution of Fe sufficiency. Thus, although individuals at high risk for ASCVD are not Fe-overloaded, they seem to benefit, metabolically and hemodynamically, from lowering of body Fe to levels commonly seen in premenopausal females.
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PMID:Effect of iron depletion on cardiovascular risk factors: studies in carbohydrate-intolerant patients. 1207 62

Elevated ferritin levels have been reported as a risk factor for coronary heart disease in Finnish and Italian studies. Studies in other populations have found no association between ferritin and cardiovascular disease raising the possibility of confounding with other cardiovascular risk factors. We determined ferritin levels, metabolic cardiovascular risk factors, C-reactive protein (CRP), anthropometric measurements and blood pressure in 815 men and women aged 26 years. In women serum ferritin correlated with CRP, waist measurement, body mass index (BMI), and triglycerides. In multiple regression analysis CRP alone was independently associated with serum ferritin. Serum ferritin in men correlated with waist measurement, BMI, triglycerides and high-density lipoprotein (HDL) cholesterol. After adjustment for the other variables, waist measurement was the only independent predictor of ferritin. Ferritin levels in young men and women are associated with obesity and serum triglycerides, HDL cholesterol in men and inflammation in women. Confounding may contribute to reports of associations between ferritin and cardiovascular disease.
Atherosclerosis 2002 Nov
PMID:Relationship of serum ferritin with cardiovascular risk factors and inflammation in young men and women. 1261 82

Thalassemic (TM) patients are subjected to peroxidative tissue injury because of continuous blood transfusions. It has been documented that circulating LDL from TM patients show marked oxidative modification, that could represent an event leading to atherogenesis. We investigated in 75 beta-TM patients the levels of oxidized LDL antibody (OLAB) to asses their correlation with total cholesterol, LDL and HDL cholesterol, triglycerides Apo A-1 and Apo B. OLAB/mg chol-LDL is greater in TM patients than healthy controls (p<0.001). No correlation was found between OLAB and age, sex of patients, mean blood consumption, mean serum ferritin, mean transaminases, PT, PTT, and fibrinogen. A significant positive correlation was found between OLAB and triglycerides in TM patients (p<0.001). Also a significant correlation was found between OLAB/mg chol-LDL and level of triglycerides in TM patients, but not with total cholesterol, LDL and HDL chols, Apo A-1 and Apo B. On the contrary in the healthy controls this correlation between OLAB and OLAB/mg chol-LDL versus triglycerides was negative and not significant. High levels of OLAB/mg chol-LDL in patients with beta-thalassemia, in absence of evident signs of atherosclerosis, suggest some regulatory mechanisms on the lipid peroxidation which modulate the deposition of ox-LDL in the macrophages and support the hypothesis that both serum iron and triglycerides are involved in the pathogenesis of LDL oxidation.
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PMID:Oxidized LDL antibodies (OLAB) in patients with beta-thalassemia major. 1222 55

Cardiovascular diseases connected with atherosclerosis are the main factor of morbidity and mortality in patients with end-stage renal failure. Hyperhomocysteinemia is a known and independent risk factor of atherosclerosis, occurring in 85-95% patients treated with hemodialysis. The aim of this study was to analyse relation between plasma level of homocysteine and chosen indicators of atherosclerosis development and also examined retrospectively cardiovascular complications in these patients. The study was carried out in 100 patients on hemodialysis who were divided into two groups: 72 patients with mild (20.74 mumol/l +/- 3.75) and 28 patients with moderate hyperhomocysteinemia (38.81 mumol/l +/- 9.81). Ultrasonographic examinations of Carotid Communis Artery Intima-Media Thickness (IMT), Ankle-Arm Blood Pressure Index (AABPI), echocardiographic parameters and biochemical examinations such as: PTH, folic acid and Vitamin B12, total protein, albumin, fibrinogen, glucose, total, LDL and HDL cholesterol, transferring, apolipoprotein B, lipoprotein (a), sodium potassium, calcium, phosphate, magnesium, iron, ferritin, urea, creatinine, uric acid and value of Hb, Ht, total iron binding capacity and transferring saturation, were performed. Patients with hypertension were divided into groups according to the number of taken anti-hypertensive drugs. Hyperhomocysteinemia was confirmed in 96% of patients. Frequency and type of acute cardiovascular complications were not related with the level of hyperhomocysteinemia. Statistically significant difference between IMT and level of hyperhomocysteinemia was observed. In patients with mild hyperhomocysteinemia IMT was 0.68 mm +/- 0.24 whereas in patients with moderate hyperhomocysteinemia 0.80 mm +/- 0.25, p < 0.036). Positive correlation between level of homocysteine and IMT (r = 0.22, p < 0.03) was noted. Based on this study, we concluded, that measurement of intima-media thickness is a good indicator of atherosclerosis development and correlates with hyperhomocysteinemia in patients on maintenance hemodialysis. It clearly confirms the role of hyperhomocysteinemia as significant risk factor of atherosclerosis in those patients.
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PMID:[Hyperhomocysteinemia and advancement of atherosclerosis in patients with chronic renal failure on maintenance hemodialysis]. 1273 67

Iron-derived reactive oxygen species (ROS) are implicated in the pathogenesis of numerous vascular disorders including atherosclerosis, microangiopathic haemolytic anaemia, vasculitis and reperfusion injury. One abundant source of redox-active iron is haem, which is inherently dangerous when released from intracellular haem proteins. The present review concerns the likely involvement of haem in vascular endothelial cell damage and the strategies used by endothelium to minimize such damage. Exposure of endothelial cells to haem greatly potentiates cell killing mediated by polymorphonuclear leukocytes and other sources of ROS. Free haem also promotes the conversion of low-density lipoprotein to cytotoxic oxidized products. If only because of its abundance, haemoglobin probably represents the most important potential source of haem within the vascular endothelium; free haemoglobin in plasma, when oxidized, can transfer haem to endothelium, thereby enhancing cellular susceptibility to oxidant-mediated injury. As a defence against such toxicity, upon exposure to free haem, endothelial cells up-regulate haem oxygenase-1 and ferritin. Haem oxygenase is a haem-degrading enzyme that opens the porphyrin ring, producing biliverdin, carbon monoxide and a most dangerous product-free redox-active iron. The latter can be controlled effectively by sequestration within ferritin, a multimeric protein with a very high capacity for storing iron. These homeostatic adjustments have been shown to be effective in the protection of endothelium against the damaging effects of exogenous haem and oxidants. The central importance of this protective system was highlighted recently by the discovery of a child diagnosed with haem oxygenase-1 deficiency, who exhibited extensive endothelial damage.
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PMID:Haem, haem oxygenase and ferritin in vascular endothelial cell injury. 1281 58


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