Thyroid hormone mediates cardioprotection against postinfarction remodeling and dysfunction through the IGF-1/PI3K/AKT signaling pathway

Abstract

BackgroundSevere cardiovascular diseases, such as myocardial infarction or heart failure, can alter thyroid hormone (TH) secretion and peripheral conversion, leading to low triiodothyronine (T3) syndrome. Accumulating evidence suggests that TH has protective properties against cardiovascular diseases and that treatment with TH can effectively reduce myocardial damage after myocardial infarction (MI). However, the potential mechanisms are not clear. This study was designed to investigate the effect of T3 pretreatment on cardiac function and pathological changes in mice subjected to MI and the underlying mechanisms. MethodsAdult male C57BL/6 mice underwent surgical ligation of the left anterior descending coronary artery (LAD) (or sham operation) to establish a myocardial infarction model. T3, BMS-754807 (inhibitor of insulin-like growth factor-1 receptor (IGF-1R)) or vehicle was administered before surgery. ResultsCompared with the MI group, the T3 pretreatment group exhibited signi cant attenuation of the myocardial infarct area, inhibition of cardiomyocyte apoptosis and brosis, and improved left ventricular function after MI. In addition, T3 exhibited an enhanced potency to stimulate angiogenesis and exert antiin ammatory effects by reducing the levels of serum in ammatory cytokines after myocardial infarction. However, all of these protective effects were inhibited by the IGF-1R inhibitor BMS-754807. Moreover, the protein expression of IGF-1/PI3K/AKT signaling-related proteins, such as IGF-1, IGF-1R, phosphorylated PI3K (p-PI3K) and p-AKT was signi cantly upregulated in MI mice that received T3 pretreatment, and BMS-754807 pretreatment blocked the upregulation of the expression of these signaling-related proteins. ConclusionT3 pretreatment can protect the heart against dysfunction post-MI through its anti-apoptotic, anti-brotic, anti-in ammatory and angiogenesis-stimulating effects, which may be mediated by the activation of the IGF-1/PI3K/AKT signaling pathway.

Analysis of lncRNA-miRNA-mRNA expression pattern in heart tissue after total body radiation in a mouse model

“…All six genes have previously been reported in the context of radiation or DNA damage response and fall into three main biological roles: cell cycle arrest, hemoglobin metabolism, and inflammatory response (Table 1 ). The prior relevant literature on Cdkn1a [ 53 , 54 ], Gdf15 [ 55 , 56 ], Ckap2 [ 57 , 58 ], Alas2 [ 59 , 60 ], Aplnr [ 61 , 62 ] and Cx3cr1 [ 63 , 64 ] are listed in Table 1 . We validated the expression of the most significantly upregulated and downregulated mRNAs in our data using RT-qPCR (Additional file 1 : Figure S1).…”

Relationship between Prognosis with Dynamic Changes of Thyroid Hormone and Cortisol Hormone in Patients with Severe Craniocerebral Injury

“…When the brain is seriously injured, intracranial hemorrhage induces an increase in intracranial pressure, ischemia, and hypoxia in brain tissue. At the same time, the activities of 5-deiodinase and nerve cell enzymes are greatly reduced, resulting in a decrease in the number of TT3 and the intake of TT4 [ 11 , 12 ]. At the same time, a severe craniocerebral injury may also induce the occurrence of stress diseases, thus, inhibiting the secretion of TSH and reducing the level of TSH [ 13 ].…”

PDE3A and GSK3B as Atrial Fibrillation Susceptibility Genes in the Chinese Population via Bioinformatics and Genome-Wide Association Analysis

“…Consistent with our pathway enrichment results, previous studies have reported that regulation of oxidative stress-related gene expression was functionally associated with PI3K/AKT signaling, which is a key profibrotic element in various tissues and was reported to be capable of activating atrial fibroblasts to differentiate into myofibroblasts [ 39 ]. Several experimental studies have sought targets to inhibit atrial remodeling by affecting oxidative stress, inflammation, and the PI3K/Akt signaling pathway [ 40 , 41 ].…”