Decreased PGC1-α levels and increased apoptotic protein signaling are associated with the maladaptive cardiac hypertrophy in hyperthyroidism

Abstract

Hyperthyroidism can lead to the activation of proteins which are associated with inflammation, apoptosis, hypertrophy, and heart failure. This study aimed to explore the inflammatory and apoptotic proteins involved in the hyperthyroidism-induced cardiac hypertrophy establishment. Male Wistar rats were divided into control and hyperthyroid (12 mg/L L-thyroxine, in drinking water for 28 days) groups. The expression of inflammatory and apoptotic signaling proteins was quantified in the left ventricle by Western blot. Hyperthyroidism was confirmed by evaluation of T3 and T4 levels, as well as cardiac hypertrophy development. There was no change in the expression of HSP70, HIF1-a, TNF-a, MyD88, p-NFjB, NFjB, p-p38, and p38. Reduced expression of p53 and PGC1-a was associated with increased TLR4 and decreased IL-10 expression. Decreased Bcl-2 expression and increased Bax/Bcl-2 ratio were also observed. The results suggest that reduced PGC1-a and IL-10, and elevated TLR4 proteins expression could be involved with the diminished mitochondrial biogenesis and anti-inflammatory response, as well as cell death signaling, in the establishment of hyperthyroidism-induced maladaptive cardiac hypertrophy.

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

“…Teixeira et al . [ 43 ] found the Bcl2 was downregulated and the BAX/Bcl2 ratio was increased in the hyperthyroid rat model. Additionally, the hyperthyroidism-induced myocardial fibrosis was associated with increased apoptotic protein signaling [ 43 ].…”

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

“…In our study, we investigated the relationship between TRP channels and ER stress sensors involved in the mechanism of hypertrophy on the basis of previous studies that suggest that hyperthyroidism causes hypertrophy (Teixeira et al, 2018, Wang et al, 2018. Using this information, the interaction between the various TRP channels and ATF-6, PERK, and IRE-1 ER stress sensors was explained using several molecular methods.…”

Toll-like receptors in cardiac hypertrophy

“…Its co-receptor myeloid differentiation protein 2 (MD2) recognizes LPS and binds TLR4, followed by the activation of the TLR4 signaling pathway ( 78 ). Additionally, hyperthyroidism, enteroviral replication, and lifestyle-related diseases directly compromise the myocardial structure and lead to inflammation through TLR4 and downstream activation of the NLRP3 inflammasome or NF-κB-dependent pathways ( 16 , 79 , 80 ). For example, postnatal growth restriction (PNGR) and hyperoxia cause intestinal dysbiosis that activates pulmonary hypertension and, subsequently, promotes right ventricular hypertrophy via the TLR4/NF-κB/IL-1β pathway ( 81 ).…”