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Both selenium deficiency and modest selenium supplementation lead to myocardial fibrosis in mice via effects on redox-methylation balance.

Publication ,  Journal Article
Metes-Kosik, N; Luptak, I; Dibello, PM; Handy, DE; Tang, S-S; Zhi, H; Qin, F; Jacobsen, DW; Loscalzo, J; Joseph, J
Published in: Mol Nutr Food Res
December 2012

SCOPE: Selenium has complex effects in vivo on multiple homeostatic mechanisms such as redox balance, methylation balance, and epigenesis, via its interaction with the methionine-homocysteine cycle. In this study, we examined the hypothesis that selenium status would modulate both redox and methylation balance and thereby modulate myocardial structure and function. METHODS AND RESULTS: We examined the effects of selenium-deficient (<0.025 mg/kg), control (0.15 mg/kg), and selenium-supplemented (0.5 mg/kg) diets on myocardial histology, biochemistry and function in adult C57/BL6 mice. Selenium deficiency led to reactive myocardial fibrosis and systolic dysfunction accompanied by increased myocardial oxidant stress. Selenium supplementation significantly reduced methylation potential, DNA methyltransferase activity and DNA methylation. In mice fed the supplemented diet, inspite of lower oxidant stress, myocardial matrix gene expression was significantly altered resulting in reactive myocardial fibrosis and diastolic dysfunction in the absence of myocardial hypertrophy. CONCLUSION: Our results indicate that both selenium deficiency and modest selenium supplementation leads to a similar phenotype of abnormal myocardial matrix remodeling and dysfunction in the normal heart. The crucial role selenium plays in maintaining the balance between redox and methylation pathways needs to be taken into account while optimizing selenium status for prevention and treatment of heart failure.

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Published In

Mol Nutr Food Res

DOI

EISSN

1613-4133

Publication Date

December 2012

Volume

56

Issue

12

Start / End Page

1812 / 1824

Location

Germany

Related Subject Headings

  • Selenoproteins
  • Selenium
  • Real-Time Polymerase Chain Reaction
  • Oxidative Stress
  • Nutrition & Dietetics
  • Myocardium
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Isoprostanes
 

Citation

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Metes-Kosik, N., Luptak, I., Dibello, P. M., Handy, D. E., Tang, S.-S., Zhi, H., … Joseph, J. (2012). Both selenium deficiency and modest selenium supplementation lead to myocardial fibrosis in mice via effects on redox-methylation balance. Mol Nutr Food Res, 56(12), 1812–1824. https://doi.org/10.1002/mnfr.201200386
Metes-Kosik, Nicole, Ivan Luptak, Patricia M. Dibello, Diane E. Handy, Shiow-Shih Tang, Hui Zhi, Fuzhong Qin, Donald W. Jacobsen, Joseph Loscalzo, and Jacob Joseph. “Both selenium deficiency and modest selenium supplementation lead to myocardial fibrosis in mice via effects on redox-methylation balance.Mol Nutr Food Res 56, no. 12 (December 2012): 1812–24. https://doi.org/10.1002/mnfr.201200386.
Metes-Kosik N, Luptak I, Dibello PM, Handy DE, Tang S-S, Zhi H, et al. Both selenium deficiency and modest selenium supplementation lead to myocardial fibrosis in mice via effects on redox-methylation balance. Mol Nutr Food Res. 2012 Dec;56(12):1812–24.
Metes-Kosik, Nicole, et al. “Both selenium deficiency and modest selenium supplementation lead to myocardial fibrosis in mice via effects on redox-methylation balance.Mol Nutr Food Res, vol. 56, no. 12, Dec. 2012, pp. 1812–24. Pubmed, doi:10.1002/mnfr.201200386.
Metes-Kosik N, Luptak I, Dibello PM, Handy DE, Tang S-S, Zhi H, Qin F, Jacobsen DW, Loscalzo J, Joseph J. Both selenium deficiency and modest selenium supplementation lead to myocardial fibrosis in mice via effects on redox-methylation balance. Mol Nutr Food Res. 2012 Dec;56(12):1812–1824.
Journal cover image

Published In

Mol Nutr Food Res

DOI

EISSN

1613-4133

Publication Date

December 2012

Volume

56

Issue

12

Start / End Page

1812 / 1824

Location

Germany

Related Subject Headings

  • Selenoproteins
  • Selenium
  • Real-Time Polymerase Chain Reaction
  • Oxidative Stress
  • Nutrition & Dietetics
  • Myocardium
  • Mice, Inbred C57BL
  • Mice
  • Male
  • Isoprostanes