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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is a need to change the policy of unselective iron supplementation during periods of life with physiologically increased cell proliferation. Levels of iron stores to be regarded as adequate during infancy and pregnancy are still not well established. Recent data support the view that it is not justified to interfere with physiological adaptations developed through millions of years by sophisticated and precisely coordinated regulation of iron absorption, utilization and storage. Recent data suggest that the chelatable intracellular iron pool regulates the expression of proteins with central importance in cellular iron metabolism (TfR, ferritin, and erythroid 5-aminolevulinic synthetase) in a coordinately controlled way through an iron dependent cytosolic mRNA binding protein, the iron regulating factor (IRF). This factor is simultaneously a sensor and a regulator of iron levels. The reduction of ferritin levels during highly increased cell proliferation is a mirror of the increased density of TfRs. An abundance of data support the vigorous competition for growth-essential iron between microbial pathogens and their vertebrate hosts. The highly coordinated regulation of iron metabolism is probably crucial in achieving a balance between the blockade of readily accessible iron to invading organisms and yet providing sufficient iron for the immune system of the host. The most evident adverse clinical effects of excess iron have been observed in immunodeficient patients in tropical countries and in AIDS patients. Excess iron also increases the risk of initiation and promotion of malignant processes by iron binding to DNA and by the iron-catalysed release of free radicals. Oxygen radicals were shown to damage critical biomolecules leading, apart from cancer, to a variety of human disease states, including inflammation and atherosclerosis. They are also involved in processes of aging and thrombosis. Recent clinical trials have suggested that the use of iron-chelators, natural and synthetic antioxidants, and anti-TfR monoclonal antibodies can contribute in retarding malignant cell proliferation. Hypoferraemia during pregnancy is--like haemodilution--an adaptation to the risks involved in the natural hypercoagulable state of pregnancy. It may also serve to prevent the risk of infections and mutagenicity in the highly proliferating tissues of the foetus. Blunted erythropoiesis has been revealed during the first 30 weeks of pregnancy by the use of the newly developed method of determining the soluble serum transferrin receptor. The lack of increase in erythropoietin levels proves that there is no hypoxia. Decreases in Hb and iron levels are parts of a physiological adaptation. As a consequence they should neither be treated nor prevented. It is stressed that whenever a widespread and ingrained routine medical intervention has to be changed it is essential to first monitor the potential health effects of the recommended change in a national policy.
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PMID:Adequate iron stores and the 'Nil nocere' principle. 824 2

The histopathology, ultrastructure, and clinicopathologic correlations in six patients with cardiac failure and iron encrustation of lung elastic tissue were examined at autopsy. Transmission electron microscopy (TEM) and energy dispersive x-ray analysis were applied to two cases. Of the group, five patients had cardiac failure due to systemic hypertension (4 patients), valvular disease (4 patients), or coronary atherosclerosis (4 patients). Biventricular failure in one patient was associated with sleep apnea. Both iron and calcium, identified by histochemical stains, impregnated degenerated alveolar and vascular elastic fibers and were associated with a foreign body reaction and focal interstitial fibrosis. Energy dispersive x-ray analysis and TEM demonstrated iron and calcium on the microfibrillar portion of elastin. Morphometry indicated vascular changes of pulmonary venous hypertension. The authors concluded that mineral deposition probably represents nonspecific precipitation of metallic ions on altered elastic fibers in patients with cardiac failure. "Mineralizing elastosis" potentially contributes to lung restriction and, occasionally, can be a source of diagnostic confusion.
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PMID:Mineralizing pulmonary elastosis in chronic cardiac failure. "Endogenous pneumoconiosis" revisited. 827 51

Vascular smooth muscle cell (VSMC) growth is a primary component of accelerated and spontaneous atherosclerosis. Previous studies have shown that iron may be involved in the control of enzymatic activities that modulate DNA synthesis in human cells. In this study the effects of the iron chelator desferrioxamine on in vitro and in vivo VSMC proliferation were tested. Rat VSMCs in culture and a rabbit model of carotid artery balloon injury were used. Desferrioxamine showed a significant inhibitory effect on [3H]thymidine incorporation in cell cultures that was antagonized by iron supplementation. Desferrioxamine also provided effective preventive myointimal VSMC proliferation as assessed by bromodeoxyuridine labeling and morphometric analysis of endoluminal stenosis. These experiments suggested that iron may be involved in the control of VSMC proliferation and that desferrioxamine may have a role in preventing VSMC growth and myointimal proliferative lesions.
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PMID:Antiproliferative effect of desferrioxamine on vascular smooth muscle cells in vitro and in vivo. 830 23

We describe an elderly patient with generalized atherosclerosis who presented with recurrent iron-deficiency anaemia. He underwent right hemicolectomy which revealed ischaemic colonic ulceration caused by cholesterol embolism. Surgery appeared to be curative. Cholesterol embolism should be considered as a possible cause of unexplained gastrointestinal blood loss in the elderly.
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PMID:Recurrent anaemia due to ischaemic colonic ulceration caused by cholesterol embolism. 832 3

Iron-derived reactive oxygen species are implicated in the pathogenesis of various vascular disorders including atherosclerosis, vasculitis, and reperfusion injury. The present studies examine whether heme, when liganded to physiologically relevant proteins as in hemoglobin, can provide potentially damaging iron to intact endothelium. We demonstrate that reduced ferrohemoglobin, while relatively innocuous to cultured endothelial cells, when oxidized to ferrihemoglobin (methemoglobin), greatly amplifies oxidant (H2O2)-mediated endothelial-cell injury. Drawing upon our previous observation that free heme similarly primes endothelium for oxidant damage, we posited that methemoglobin, but not ferrohemoglobin, releases its hemes that can then be incorporated into endothelial cells. In support, cultured endothelial cells exposed to methemoglobin--in contrast to exposure to ferrohemoglobin, cytochrome c, or metmyoglobin--rapidly increased their heme oxygenase mRNA and enzyme activity, thereby supporting heme uptake; ferritin production was also markedly increased after such exposure, thus attesting to eventual incorporation of Fe. These cellular methemoglobin effects were inhibited by the heme-scavenging protein hemopexin and by haptoglobin or cyanide, agents that strengthen the liganding between heme and globin. If the endothelium is exposed to methemoglobin for a more prolonged period (16 hr), it accumulates large amounts of ferritin; concomitantly, and presumably associated with iron sequestration by this protein, the endothelium converts from hypersusceptible to hyperresistant to oxidative damage. We conclude that when oxidation of hemoglobin facilitates release of its heme groups, catalytically active iron is provided to neighboring tissue environments. The effect of this relinquished heme on the vasculature is determined both by extracellular factors--i.e., plasma proteins, such as haptoglobin and hemopexin--as well as intracellular factors, including heme oxygenase and ferritin. Acutely, if both extra- and intracellular defenses are overwhelmed, cellular toxicity arises; chronically, when ferritin is induced, resistance to oxidative injury may supervene.
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PMID:Endothelial-cell heme uptake from heme proteins: induction of sensitization and desensitization to oxidant damage. 841 93

Our views on paediatric nutrition have considerably changed during the last 20 years. Some hereditary metabolic diseases testify to the remarkable efficacy of a specific preventive dietetics avoiding the development of mental retardation. Although certain deficiencies (in iron, fluorine, folates, vitamin D) are persisting in France, the major problems concern the prevention in childhood of allergy, obesity, atherosclerosis, high blood pressure, osteoporosis and even certain cancers, all diseases which play a crucial role in the morbidity and mortality of adults. Numerous uncertainties still exist, but in the present state of our knowledge we can already develop some recommendations which should replace the much abusive publicity that prevails in the information given to the public.
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PMID:[Towards preventive dietetics in children]. 850 35

Diabetic patients have high levels of glycated LDL. Although glycated LDLs are implicated in the development of atherosclerosis in such patients, convincing data are lacking. We observed release of superoxide radicals (O2-) from mouse resident peritoneal macrophages stimulated by an oxidized/glycated LDL by using a highly sensitive and specific chemiluminescence method. Oxidized/glycated LDL was achieved by an addition of low concentration of Fe3+ to glycated LDL. Macrophages took up an appreciable amount of the glycated LDL oxidized by iron, leading to the development of foam cells, while they did not take up untreated glycated LDL or the native LDL. These observations clearly indicate that the oxidized/glycated LDL reacts well with macrophages. Since an oxidation of glycated LDL may occur in vivo, the oxidized/glycated LDL might play an important role in atherogenesis.
Atherosclerosis 1995 Nov
PMID:Release of superoxide radicals by mouse macrophages stimulated by oxidative modification of glycated low density lipoproteins. 857 19

Oxidative modification of human low-density lipoprotein (LDL) is thought to play a major role in the development of atherosclerosis. Free hemin, hemoglobin, myoglobin, and horseradish peroxidase (HRP) were reported in different studies as promoters of LDL lipid oxidation. Based on our previous finding that hemin induced oxidative crosslinking of the LDL protein, apolipoprotein B (apo B) (Y. I. Miller and N. Shaklai (1994) Biochem. Mol. Biol. Int. 34, 1121-1129), we compared the ability of free hemin and the above hemoproteins to induce peroxidation modification of apo B using SDS-PAGE. The levels of the final products of lipid peroxidation were determined as thiobarbituric acid-reactive substances. Hemoglobin and myoglobin were found to be as active as free hemin and all these were much more active than the classic peroxidase HRP. Moreover, the products of oxidized apo B differed: hemoglobin, myoglobin, and hemin induced mostly covalent aggregates, while HRP caused fragmentation of apo B. Hemoglobin reactivity was expressed at low H2O2 concentrations even in the absence of molecular oxygen. Desferal, along with other antioxidants, inhibited the hemoglobin-induced LDL oxidation independently of its iron-chelating property. The high peroxidative reactivity of hemoglobin is explained by its ability (unlike HRP) to transfer the oxidative equivalents from the heme active site, through the globin, to LDL. The apo B radicals thus formed are terminated, yielding intermolecular crosslinked protein. It is suggested that small amounts of the highly reactive hemoglobin in plasma, suffice to trigger LDL protein oxidation (along with its lipid oxidation), thereby inflict the atherosclerosis precondition.
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PMID:Hemoglobin induced apolipoprotein B crosslinking in low-density lipoprotein peroxidation. 861 Oct 31

New atherosclerosis causative factors and preventive modalities have been identified. Atherogenic factors include lipid oxidation products, such as cholesterol oxidation products, malonaldehyde and other aldehydes; trans-fatty acids; some saturated fatty acids (lauric, myristic and possibly palmitic acids); and myristic acid plus cholesterol. Lipid oxidation products are well suited to induce arterial damage, based on their known cytotoxic effects; evidence also indicates the possibility of plaque promotion and stimulation of thrombogenesis. Anti-atherogenic factors include antioxidants, fish oils and other polyunsaturates (if protected from oxidation), fibre and trace minerals such as copper, manganese, selenium and zinc. Iron is unique, being considered as both a potential promoter of atherosclerosis (component of ferritin, conceivably inducing lipid oxidation) and a possible anti-atherogenic component (of antioxidant enzyme catalase). It is apparent that an entire new series of research challenges has been uncovered.
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PMID:Atherogenic and anti-atherogenic factors in the human diet. 866 Apr

This article reviews our current understanding of the mechanisms of low-density lipoprotein (LDL) oxidation and the potential role of oxidized lipoproteins in atherosclerosis. Studies in hypercholesterolemic animal models indicate that oxidation of LDL is likely to play an important role in atherogenesis. Epidemiological investigations further suggest that the dietary intake of antioxidants is inversely associated with the risk of vascular disease, suggesting that oxidized LDL may be important in human atherosclerosis. By activating inflammatory events, oxidized lipoproteins may contribute to all stages of the atherosclerotic process. Lipoprotein oxidation is promoted by several different systems in vitro, including free and protein-bound metal ions, thiols, reactive oxygen intermediates, lipoxygenase, peroxynitrite, and myeloperoxidase. Intracellular proteins that bind iron or regulate iron metabolism might also play an important role. The physiologically relevant pathways have yet to be identified, however. We assess recent findings on the effects of antioxidants in vivo and suggest potential strategies for inhibiting oxidation in the vessel wall.
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PMID:The role of oxidized lipoproteins in atherogenesis. 872 15


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