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 endoplasmic reticulum (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. Twenty 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 (T4) for 4 weeks. At the end of the fourth week, the serum-free triiodothyronine (T3), T4, and thyroid-stimulating hormone (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, activating transcription factor 6 (ATF-6), inositol-requiring kinase 1 (IRE-1), and TRPC1, which play a significant role in cardiac hypertrophy caused by hyperthyroidism, showed increased activation. Moreover, TOS and serum-free T3 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 of ATF-6, IRE-1, and TRPC1-induced deterioration of the Ca2+ ion balance leads to hypertrophy in hyperthyroidism due to heart failure.