Selenistasis: Epistatic Effects of Selenium on Cardiovascular Phenotype

Abstract

Although selenium metabolism is intricately linked to cardiovascular biology and function, and deficiency of selenium is associated with cardiac pathology, utilization of selenium in the prevention and treatment of cardiovascular disease remains an elusive goal. From a reductionist standpoint, the major function of selenium in vivo is antioxidant defense via its incorporation as selenocysteine into enzyme families such as glutathione peroxidases and thioredoxin reductases. In addition, selenium compounds are heterogeneous and have complex metabolic fates resulting in effects that are not entirely dependent on selenoprotein expression. This complex biology of selenium in vivo may underlie the fact that beneficial effects of selenium supplementation demonstrated in preclinical studies using models of oxidant stress-induced cardiovascular dysfunction, such as ischemia-reperfusion injury and myocardial infarction, have not been consistently observed in clinical trials. In fact, recent studies have yielded data that suggest that unselective supplementation of selenium may, indeed, be harmful. Interesting biologic actions of selenium are its simultaneous effects on redox balance and methylation status, a combination that may influence gene expression. These combined actions may explain some of the biphasic effects seen with low and high doses of selenium, the potentially harmful effects seen in normal individuals, and the beneficial effects noted in preclinical studies of disease. Given the complexity of selenium biology, systems biology approaches may be necessary to reach the goal of optimization of selenium status to promote health and prevent disease.

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].…”

Ulcerative Colitis and Crohn’s Disease Are Associated with Decreased Serum Selenium Concentrations and Increased Cardiovascular Risk

“…Importantly, IBDs have been associated with an increased risk of colon cancer [1,7]. However, despite evidence on the importance of Se and selenoproteins for the cardiovascular (CV) system due to their antioxidant functions [8,9,10] and the role of Se-enriched diets in reducing colon cancer risk development [11], few data are available on the influence of Se in IBDs. Se supplementation has been reported to protect against tissue damage in chemically-induced UC by modifying the expression of genes involved in the mitochondrial regulation of cell death [12].…”

Personalized Hypertension Management in Practice

“…The polypill, which currently addresses a number of cardiovascular risk factors including hypertension, is however reductionistic, as are public health concepts of universal dietary supplementation or restrictions [76,77]. Although effective to a degree, these measures cannot address the wide population variability in response to diet, exercise and medication [46].…”