New Perspectives on Selenium and Selenoproteins in Cardiomyopathy

Selenium (Se) is an indispensable micronutrient for a number of biologic processes, being integrated as a selenocystein in the primary structure of selenoproteins [1]. Strikingly, Se deficiency has been well recognized as a contributing factor to pathological conditions including heart disease, neuromuscular disorders, cancer, male infertility, inflammation and other disorders [1].

The human genome contains 25 genes, coding selenocysteine containing proteins termed as Selenoproteins [2, 3]. The selenocystein is synthesized and inserted into proteins during the translational process of the mRNA by a mechanism which involves converting a termination codon viz. UGA. These proteins are involved in a variety of functions, most notably redox homeostasis. Selenoprotein enzymes with known functions are designated according to their function viz TXNRD1, TXNRD2 and TXNRD3 [thioredoxin reductase], GPX1, GPX2, GPX4 and GPX6 [glutathione peroxidases], DIO1, DIO2 and DIO3 [Iodothyronine deiodinases, MSRB1 [Methionine sulfoxide reductase B1] and SEPHS2 [Selenophosphate synthetase 2]. Selenoproteins without known functions have traditionally been denoted by SEL or SEP. Recently, HUGO gene nomenclature committee (HGNC) has adopted a root symbol format, where selenoprotein genes are designated with “SELENO” followed by a letter [3]. This nomenclature applies SELENOF (Selenoprotein F), SELENOH (Selenoprotein H), SELENOP (Selenoprotein P), and so on [4].

It is well documented that severe selenium deficiency is fraternized with cardiomyopathy in humans [5]. For instance, Keshan disease (KD) is an endemic dilated cardiomyopathy with high mortality rates from Keshan county of China [6]. The clinical manifestations of KD include acute or chronic episodes of heart disease, characterized by cardiogenic shock, congestive heart failure and arrhythmia along with cardiomegaly. Moreover, a meta-analysis of 16 observational studies exhibited an inverse association between cardiovascular events and selenium status [7]. In fact sufficient selenium levels are essential in order to synthesize the required amount of selenoproteins. Otherwise, lessened amount of selenoproteins may have consequences such as cardiomyopathy [8]. These proteins also play an important function in antioxidant defense, thyroid metabolism, proteins folding and immunity. Strikingly, the selenoproteins viz TXNRDs, GPXs, MSRB1 and others . (Selenoprotein P, O, K, N, S etc.) involve in redox regulation and antioxidant activity [9]. These proteins are associated with cardiovascular diseases. Selenoprotein P (SELENOP) is the main carrier of selenium in the blood. The patient with lower SELENOP level had greater risk for heart failure. Selenoprotein P had dual functions providing selenium for tissues and antioxidant defense capabilities. Moreover, several polymorphisms in SELENOP gene are associated with susceptibility of tumors viz. breast cancer, colorectal cancer and prostate cancer [1].

In conclusion, Selenoproteins may exert their beneficial effects not only locally in cardiac tissues but also systematically. They may do so through several mechanisms that are discombobulated in cardiomyopathy including maintaining healthy mitochondria, redox regulation, anti-inflammatory effects, improving immune cell functionality, improve thyroid metabolism and reducing ER stress. Since heart failure is a systematic disease. All together, these effects suggest that selenium supplementation may offer additional systematic improvements [10]. Therefore, well-designed randomized clinical trials, focussing on the role of selenoproteins in different pathologies viz. neuromuscular, cardiovascular, neurodegenerative, inflammatory, endocrine can provide the strategy for their use in treatment or prevention of various diseases.