Atherogenesis and iron: from epidemiology to cellular level

Vinchi, Francesca; Muckenthaler, Martina U.; Silva, Milene C. Da; Balla, G; Balla, JÃ3zsef; Jeney, V.

doi:10.3389/fphar.2014.00094

Cited by 133 publications

(129 citation statements)

References 230 publications

(284 reference statements)

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“…There is some evidence that with increasing age, high circulating iron levels worsen the atherosclerotic phenotype [9]. Macrophages in the vessel wall can accumulate iron from increased destruction of RBCs or by disturbed iron homeostasis, leading to increased production of ROS and decreased efflux of cholesterol.…”

Section: Clinical Consequences Of Iron Overload In Mdsmentioning

confidence: 99%

Iron overload in myelodysplastic syndromes (MDS)

Gattermann

2017

Int J Hematol

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Iron overload (IOL) starts to develop in MDS patients before they become transfusion-dependent because ineffective erythropoiesis suppresses hepcidin production in the liver and thus leads to unrestrained intestinal iron uptake. However, the most important cause of iron overload in MDS is chronic transfusion therapy. While transfusion dependency by itself is a negative prognostic factor reflecting poor bone marrow function, the ensuing transfusional iron overload has an additional dose-dependent negative impact on the survival of patients with lower risk MDS. Cardiac dysfunction appears to be important in this context, as a consequence of chronic anemia, age-related cardiac comorbidity, and iron overload. Another potential problem is iron-related endothelial dysfunction. There is some evidence that with increasing age, high circulating iron levels worsen the atherosclerotic phenotype. Transfusional IOL also appears to aggravate bone marrow failure in MDS, through unfavorable effects on mesenchymal stromal cells as well a hematopoietic cells, particularly erythroid precursors. Patient series and clinical trials have shown that the iron chelators deferoxamine and deferasirox can improve hematopoiesis in a minority of transfusion-dependent patients. Analyses of registry data suggest that iron chelation provides a survival benefit for patients with MDS, but data from a prospective randomized clinical trial are still lacking.

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Section: Clinical Consequences Of Iron Overload In Mdsmentioning

confidence: 99%

Iron overload in myelodysplastic syndromes (MDS)

Gattermann

2017

Int J Hematol

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“…Despite the large number of studies having been published to date, the role of iron in CVD still generates a fair amount of debate (26). However, the impact of iron on atherosclerosis is still debated.…”

Section: Discussionmentioning

confidence: 99%

Iron concentrations in atherosclerotic plaque and serum in patients with carotid atherosclerosis

Tasić¹,

Tasić²,

Veselinović³

et al. 2015

Acta Physiologica Hungarica

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The aim of this study was to investigate the iron concentrations in serum and carotid plaque in patients with different morphology of carotid atherosclerotic plaque and compared with other metal ions. Carotid endarterectomy due to the significant atherosclerotic stenosis was performed in 91 patients. Control group consisted of 27 patients, without carotid atherosclerosis. Atherosclerotic plaques were divided into four morphological groups, according to ultrasonic and intraoperative characteristics. Iron, copper and zinc concentration in plaque, carotid artery and serum were measured by spectrophotometry. Serum iron concentrations were higher in patients with hemorrhagic plaques in comparison to the control group (4.7 μmol/l ± 1.2 vs. 2.1 μmol/l ± 0.8, p < 0.05). Iron concentrations were higher in patients with hemorrhagic plaques in comparison to fibrolipid plaques (72.1 ± 14.3 μg/g vs. 39.3 ± 22.9 μg/g; p < 0.05). Negative significant correlation was found for zinc in serum and plaque iron concentration in patients (p < 0.05). We also demonstrated positive significant correlation for copper and iron in serum (p < 0.05). The data obtained in the current study are consistent with the hypothesis that high iron levels may contribute to atherosclerosis and its complications as factors in a multifactorial disease.Keywords: carotid plaque, atherosclerosis, iron, zinc, copperOver the last 30 years, several studies in animals and humans assessed the effect of increased body iron levels on atherosclerosis, yielding conflicting results.Iron is a key element in many biochemical processes and shortage of iron causes damage to cells and organs. On the other hand, excess iron could be harmful because it is able to catalyse the formation of highly reactive oxygen and hydrogen radicals when present in the unbound state. Transition metal ions, established catalysts of protein, lipid and DNA oxidation, are present at elevated levels in human atherosclerotic plaques, and in some animal models, consistent with the hypothesis that metal ions contribute to both plaque formation and its destabilization (19,21,23), though the role of metal ions remains controversial (16,29).Epidemiological studies have reported an increased incidence of cardiovascular disease (CVD) in subjects with overt iron overload (7,8,19). Recent studies on cardiovascular evaluation and outcome in high-versus low-frequency blood donors have demonstrated improvements in surrogate markers of vascular health such as decreased oxidative stress, and

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“…Iron mediates the oxidative modification of LDL, an important contributing factor to the pathogenesis of atherosclerosis [510] . Cholesterol levels in atherosclerotic lesions correlated with iron deposits [511] , and within the plaque, iron deposition and ferritin induction have been observed in endothelial cells and macrophages in early human lesions, and additionally in VSMCs in late lesions [503] . Interestingly, in hypercholesterolemic pigs, Gerrity [512] found that monocytes were adherent to the lesion areas of aortic endothelium, in endothelial junctions, and in the intima.…”

Section: Atherosclerosismentioning

confidence: 92%

“…According to the "iron hypothesis", iron overload is believed to be detrimental for the cardiovascular system, thus promoting atherosclerosis development and progression [503,504] . Excess of iron generates oxidative stress that hallmarks neurodegenerative diseases and atherosclerosis, a frequent disorder of aging [505] .…”

Section: Atherosclerosismentioning

confidence: 99%

“…Lf and transferrin maintain Fe 3+ in a soluble and stable oxidation state, avoiding the generation of toxic free hydroxyl radicals [514] . Hemolysis is often a result between the interaction of erythrocytes and mature atheromas resulting in the transition of ferrous to ferric forms of Hb which additionally leads to lipid peroxidation [519] , triggering endothelial activation, smooth muscle cell proliferation and macrophage activation [503] . Oxidized form Hb can also act as a proinflammatory agonist that targets vascular endothelial cells [520] .…”

Section: Atherosclerosismentioning

confidence: 99%

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