Effects of Thyroid Hormones on Electrical and Mechanical Parameters of the Heart
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Effects of Thyroid Hormones on Electrical and Mechanical Parameters of the Heart I. K. Dzhumaniiazovaa, * and O. V. Smirnovaa, ** a
Moscow State University, Moscow, 119991 Russia *e-mail: [email protected] **e-mail: [email protected]
Received December 28, 2019; revised March 4, 2020; accepted April 19, 2020
Abstract—Despite the fact that effects of thyroid hormones were noticed back in the 80s, the underlying molecular mechanisms have not yet been elucidated. Current review summarizes years of investigations upon molecular targets for the action of thyroid hormones, leading to changes in the electrical and mechanical activity of the heart; changes in hemodynamics, affecting the functioning of the heart muscle, are also touched. Keywords: thyroid hormones, the heart, cardiomyocytes, ion currents, fibroblasts, macrophages DOI: 10.1134/S0362119720050047
Thyroid gland produces thyroid hormones that are the great importance for the organism at all ontogenesis stages. They participate in the development of the central nervous system and organize the lineal growth during early ontogenesis [1]. Thyroxine (T4) and triiodothyronine (T3) normalize metabolism and thermogenesis of the adult organism; they regulate the work of different organ systems, including the cardiovascular [2, 3]. Nuclear receptors for thyroid hormones underpin their effect and include two types receptors (TRα and TRβ) encoded by different genes [4]. T3 changes the expression level of target genes by acting on these receptors, these in turn changes cells’ activity [2, 4, 5]. Thyroid hormones have non-genome effects also: they change the cytoskeleton and activity level of mitochondria, plasma membrane exchangers, and ion channels [4]. Thyroid hormones have wide effects on organism, thus they alter electrical and mechanical parameters of the heart [2–5]. Hormones change the cardiac activity by the direct action on cardiomyocytes and by indirect effects on the peripheral resistance [3, 6]. We described these direct and indirect effects of T3 and T4 separately. This review is aimed to collect and systemize information about molecular and integral mechanisms of T3 action on the structure and function of the mammalian heart. DIRECT EFFECTS OF THYROID HORMONES The heart is a complex organ. It consists not only of cardiomyocytes but also of different cell types—fibro-
blasts, macrophages, smooth muscle cells, endothelial cells, etc [7, 8]. The work of these cells changes when hormones act on them. We should take a closer look at the action of T3 and T4 on all these cell types to understand better the influence of thyroid hormones on heart activity. This review is focused on the effects of thyroid hormones on cardiomyocytes, fibroblasts and macrophages because they make up to about 90–95% of the human heart [7]. The Effect of Thyroid Hormones on Cardiomyocytes In contrast to human cardiomyocytes, rodents’ cardiomyocytes lack (or have trace amounts of) the deiodinase type II [9]. That is why T4 converts slightly into active T3 in rat and mouse cardiomyocy
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