Iron Overload or Oxidative Stress? Insight into a Mechanism of Early Cardiac Manifestations of Asymptomatic Hereditary Hemochromatosis Subjects with C282Y Homozygosity

Shizukuda, Yukitaka; Tripodi, Dorothy; Rosing, Douglas R.

doi:10.1007/s12265-016-9704-2

Cited by 12 publications

(9 citation statements)

References 5 publications

(11 reference statements)

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“…Iron is a strong prooxidant transition element. Due to this feature, it can cause cellular damage in different tis sues by generating reactive oxygen species [24,37]. Another possible mechanism could be based on Hevi et al's research [38].…”

Section: T a B L E 1 B -Distribution Of Parameters Between Gendersmentioning

confidence: 99%

The relationship between serum ferritin levels and serum lipids and HDL function with respect to age and gender

Elli̇dağ¹,

Eren²,

Akdağ³

et al. 2016

Ukr.Biochem.J.

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Elevated serum ferritin (SFer) levels have been associated with chronic diseases such as coronary heart disease and diabetes mellitus type 2. The aim of this study was to examine the relationship between SFer levels and serum lipid parameters, and how this relation changes in terms of age and gender. Additionally, we investigated a possible relationship between SFer levels and high-density lipoprotein (HDL) function. SFer levels and lipid panel (total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C) and HDL-C) of 4205 people (3139 women, 1066 men) were examined retrospectively. Study population was classified according to age and gender. Separately, 100 subjects (52 women, 48 men) were randomly recruited to investigate the relation between SFer levels, and HDL dependent paraoxonase-1 (PON1) and arylesterase (ARE) activities. In all age groups, women’s SFer levels were found to be significantly lower and HDL-C levels significantly higher compared to men. In the 50-70 ages range, TC and LDL-C levels of women were found to be significantly higher than those of men (P < 0.01). SFer levels tended to increase with age in women. Correlation analyses revealed a negative correlation between levels of SFer and HDL-C, while positive correlations existed between levels of SFer, and TC, TG and LDL-C. There was no significant correlation between SFer levels and PON1 or ARE activities. The finding that increased SFer levels are accompanied by increased serum TC, TG and LDL-C levels may help us to explain the increased risk of metabolic disorders and cardiovascular disease in postmenopausal women.

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Section: T a B L E 1 B -Distribution Of Parameters Between Gendersmentioning

confidence: 99%

The relationship between serum ferritin levels and serum lipids and HDL function with respect to age and gender

Elli̇dağ¹,

Eren²,

Akdağ³

et al. 2016

Ukr.Biochem.J.

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“…We also found that the chronically treated HH patients showed significantly elevated oxidative stress levels despite therapeutic biochemical iron levels . In view of these observations, elevated oxidative stress may contribute to the increased ectopy of this patient group . Importantly, these patients showed normal left ventricular systolic function and did not fill the criteria for grade I or above left ventricular diastolic dysfunction, negating the influence of cardiac dysfunction caused by IO .…”

Section: Mechanismsmentioning

confidence: 60%

“…In human studies, interestingly, the association of elevated oxidative stress with atrial fibrillation has been documented in the postsurgical period . This is an interesting finding because atrial fibrillation is reported to be also associated with IO in humans as well, in which oxidative stress is also elevated …”

Section: Mechanismsmentioning

confidence: 82%

Iron overload and arrhythmias: Influence of confounding factors

Shizukuda

Rosing

2019

Journal of Arrhythmia

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Arrhythmias as a cardiac complication of iron overload (IO) have been well described for decades in the clinical literature. They are assumed to be directly associated with the myocardial accumulation of iron. However, the influence of heart failure and elevated oxidative stress, which are major arrhythmogenic confounding factors associated with IO on arrhythmias, has not been critically reviewed in the published literature. A comprehensive narrative review of published articles in PubMed was conducted to address the influence of confounding factors of IO on arrhythmias. The previous data may have been largely confounded by the other cardiac complications of IO, particularly heart failure. The previous studies on IO‐related arrhythmias lack proper age‐gender–matched control subjects and/or comparison groups with properly controlled confounding factors to assess accurately their etiology and clinical significance. Given the above considerations, further mechanistic investigations to clarify the etiology and clinical relevance of IO‐induced arrhythmias are needed. In addition, investigations to develop arrhythmia management strategy specific to IO, are warranted.

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“…There are cases of cardiac arrest, syncope, and life-threatening ventricular arrhythmias that have been linked to hereditary hemochromatosis 13, 14. The mutation C282Y carried by the patient is the most commonly detected pathogenic alteration related to hemochromatosis in white populations and could have variable phenotypic expression and penetrance 13, 15. There are preliminary reports suggesting that this mutation could be associated with increased arrhythmic burden even in the absence of macroscopic iron deposition in the myocardium 15 .…”

Section: Discussionmentioning

confidence: 99%

“…The mutation C282Y carried by the patient is the most commonly detected pathogenic alteration related to hemochromatosis in white populations and could have variable phenotypic expression and penetrance 13, 15. There are preliminary reports suggesting that this mutation could be associated with increased arrhythmic burden even in the absence of macroscopic iron deposition in the myocardium 15 . Although the ultimate diagnosis in this patient remains “idiopathic” VF with unknown causes, the exclusion of a role for the LMNA variant carries important implications in terms of cascade screening and calls for caution in the assessment of genetic variants in the absence of careful functional characterization.…”

Section: Discussionmentioning

confidence: 99%