Cardiac hypertrophy caused by hyperthyroidism in rats: the role of ATF-6 and TRPC1 channels

Abstract

Hyperthyroidism influences the development of cardiac hypertrophy. Transient receptor potential canonical channels (TRPCs) and ER stress are regarded as critical pathways in cardiac hypertrophy.Hence, we aimed to identify the TRPCs associated with ER stress in hyperthyroidism-induced cardiac hypertrophy.20 adult Wistar albino male rats were used in the study.The control group was fed with standard food and tap water. The group with hyperthyroidism was also fed with standard rat food, along with tap water that contained 12 mg/L of thyroxine for four weeks.At the end of the fourth week, the serum-free T3, T4, and TSH levels of the groups were measured. The left ventricle of each rat was used for histochemistry, immunohistochemistry, western blot, total antioxidant capacity (TAC), and total oxidant status (TOS) analysis. 
 As per our results, ATF-6, IRE-1, and TRPC1, which play a significant role in cardiac hypertrophy caused by hyperthyroidism, showed increased activation. Moreover, TOS and fT3 levels increased, while TAC and TSH levels decreased. 
 With the help of the literature review in our study, we could, for the first time, indicate that the increased activation, in particular of ATF-6, IRE-1, and TRPC1-induced deterioration of the Ca2+ ion balance, leads to hypertrophy in hyperthyroidism due to heart failure.

Diosmetin‐7‐O‐β‐D‐glucopyranoside suppresses endothelial–mesenchymal transformation through endoplasmic reticulum stress in cardiac fibrosis

“…41 The deterioration of Ca 2+ ion balance induced by ATF6, IRE1 and PERK leads to myocardial hypertrophy caused by hyperthyroidism. 43 At the same time, the nucleotide-binding domain of GRP78 dissociates from the lumen domain of IRE1 and PERK, leading to further activation of UPR. 44 As ER stress becomes chronic or excessive, it may induce the proapoptotic transcription factor CHOP, which may lead to apoptosis.…”

“…It is worth noting that the activation of ATF6 and IRE1α can directly upregulate the transcription or processing of mRNA of UPR genes, 41,42 while PERK inhibits the activation of ER and reduces the protein load of ER 41 . The deterioration of Ca 2+ ion balance induced by ATF6, IRE1 and PERK leads to myocardial hypertrophy caused by hyperthyroidism 43 . At the same time, the nucleotide‐binding domain of GRP78 dissociates from the lumen domain of IRE1 and PERK, leading to further activation of UPR 44 .…”

Inhibitory effect of (pro)renin receptor decoy inhibitor PRO20 on endoplasmic reticulum stress during cardiac remodeling

“…Frontiers in Pharmacology frontiersin.org 10 initiation and decreases the protein load on the ER (Lee et al, 2002). ATF-6, IRE1 and PERK-induced deterioration of the Ca 2+ ion balance leads to cardiac hypertrophy caused by hyperthyroidism (Bektur Aykanat et al, 2021), and PERK was also essential during the experiments for avoiding TAC-induced congestive HF (Liu et al, 2014). In line with these findings, we found that there was a remarkable change in the activation of IRE1, PERK and ATF-6 in Ang II-treated CMs and CFs, suggesting that the ER stress induced by Ang II participated in cardiomyocyte hypertrophy and fibroblast activation.…”

Effects of gas signaling molecule SO2 in cardiac functions of hyperthyroid rats

“…In contrast, myocardial fibrosis is a key factor affecting the progression of HTC. THs induce endoplasmic reticulum stress (ERS) [ 6 ] and apoptosis in cardiomyocytes [ 7 ] while increasing the force and speed of myocardial contraction [ 8 ] and the burden on the heart. Thus, it can lead to cardiac hypertrophy and left ventricular dysfunction [ 9 ], resulting in heart failure [ 10 , 11 ] and dilated cardiomyopathy [ 12 ].…”