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

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Abstract

Hereditary hemochromatosis (HH) is a genetic disorder which affects the heart due to systemic iron overload and concomitant elevated oxidative stress. Increasing numbers of patients are diagnosed at an asymptomatic stage due to genetic testing. Subclinical abnormal left ventricular diastolic function (LVDF) and increased arrhythmias are noted in this population; however, the mechanism leading to these observances has not been well understood. In this study, we assessed the relationship between arrhythmia activity and biomarkers of oxidative stress and iron overload in order to elucidate the role of oxidative stress in this population since we observed a significant association with LVDF previously. A significant correlation between plasma malondialdehyde, a biomarker of oxidative stress, and supraventricular arrhythmia activity without a significant association with iron overload was identified (n = 22). Our findings further highlight a possible role of oxidative stress in early cardiac manifestations of HH. Further investigation is warranted to assess this role.

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Abbreviations

HH:

Hereditary hemochromatosis

LVDF:

Left ventricular diastolic function

LV:

Left ventricle

NHLBI:

National Heart, Lung, and Blood Institute

GSH:

Glutathione

SOD:

Superoxide dismutase

MDA:

Malondialdehyde

SVE:

Supraventricular ectopic beat

VE:

Ventricular ectopic beat

References

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Acknowledgments

We thank Dr. Tammy T. Nguyen and Mr. Gilberto Botello at the Cardiopulmonary Branch, NHLBI, for assisting biochemical assays. We thank Ms. Gloria Zalos, RN for analyzing Holter ECG data. We thank Dr. Charles D. Bolan, Dr. Susan F. Leitman, and Ms. Yu-Ying Yau, RN at the Department of Transfusion Medicine, NHLBI for recruiting our subjects.

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Authors and Affiliations

  1. Cardiopulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA

    Yukitaka Shizukuda, Dorothy J. Tripodi & Douglas R. Rosing

  2. Division of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA

    Yukitaka Shizukuda

  3. Cincinnati VA Medical Center, Cincinnati, OH, USA

    Yukitaka Shizukuda

Authors
  1. Yukitaka Shizukuda
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  2. Dorothy J. Tripodi
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  3. Douglas R. Rosing
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Corresponding author

Correspondence to Yukitaka Shizukuda.

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Source of Funding

This study was funded by the intramural funds of the National, Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health.

Conflict of Interest

The authors declare that they have no conflict of interest.

Human Subjects/Informed Consent Statement

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the 1964 Helsinki Declaration as revised in 2000. Informed consent was obtained from all individual participants for being included in this study.

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Associate Editor Daniel P. Judge oversaw the review of this article

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Shizukuda, Y., Tripodi, D.J. & Rosing, D.R. Iron Overload or Oxidative Stress? Insight into a Mechanism of Early Cardiac Manifestations of Asymptomatic Hereditary Hemochromatosis Subjects with C282Y Homozygosity. J. of Cardiovasc. Trans. Res. 9, 400–401 (2016). https://doi.org/10.1007/s12265-016-9704-2

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  • DOI: https://doi.org/10.1007/s12265-016-9704-2

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