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

Abstract

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. Conclusions 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.

Optimal Serum Selenium Concentrations Are Associated with Lower Depressive Symptoms and Negative Mood among Young Adults

“…A U-shaped curve was also reported by Bleys et al (24) in relation to selenium status and all-cause mortality (>150 mg/L). Animal research also reported a similar U-shaped curve in relation to type 2 diabetes risk (25) and heart function (26). SeleniumÕs role as an antioxidant may help to explain these findings.…”

High levels of plasma selenium are associated with metabolic syndrome and elevated fasting plasma glucose in a Chinese population: A case-control study

“…The mechanism underlying the adverse effects on glucose metabolism could be that excess selenium, as well as insufficient selenium, damage the redox-methylation balance through the methionine-homocysteine cycle and so lead to excessive expression of GPx1 [36,37]. The results from animal studies have demonstrated that overexpression of GPx1 is associated with insulin resistance, hyperglycemia and obesity [38,39].…”

The role of dietary selenium in inflammation and immunity

“…This same review did not support a role for Se supplementation to promote cardiovascular health (Rees et al, 2013). Heart inflammation in the context of Se status is important given that both Se deficiency and modest Se supplementation lead to a similar phenotype of abnormal myocardial matrix remodeling and dysfunction in the normal heart in mice, indicating it needs to be taken into account while optimizing Se status for prevention and treatment of heart failure (Metes-Kosik et al, 2012). In lieu of recommending Se supplementation for the general public for improving overall immunity or reducing chronic inflammation, future studies may lead to the use of this supplement for periodic treatment of specific disorders.…”