Abstract
AimsSevere 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). Our aim is to investigate the effect of T3 pretreatment on cardiac function and pathological changes in mice subjected to MI and the underlying mechanisms. Main methodsAdult male C57BL/6 mice underwent surgical ligation of the left anterior descending coronary artery (LAD) (or sham operation) to establish MI model. T3, BMS-754807 (inhibitor of insulin-like growth factor-1 receptor (IGF-1R)) or vehicle was administered before surgery. Key findingsCompared with the MI group, the T3 pretreatment group exhibited significant attenuation of the myocardial infarct area, inhibition of cardiomyocyte apoptosis and fibrosis, and improved left ventricular function after MI. In addition, T3 exhibited an enhanced potency to stimulate angiogenesis and exert anti-inflammatory effects by reducing the levels of serum inflammatory cytokines after MI. 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 significantly upregulated in MI mice that received T3 pretreatment, and BMS-754807 pretreatment blocked the upregulation of the expression of these signaling-related proteins. SignificanceT3 pretreatment can protect the heart against dysfunction post-MI, which may be mediated by the activation of the IGF-1/PI3K/AKT signaling pathway.
Highlights
Acute myocardial infarction (AMI) is a serious ischemic heart disease with significant morbidity and mortality worldwide[1]
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 significantly upregulated in MI mice that received T3 pretreatment, and BMS-754807 pretreatment blocked the upregulation of the expression of these signaling-related proteins
The results of this study showed that the serum levels of tT3, free T3 (fT3), tT4 and fT4 were significantly decreased and TSH increased after MI, which was consistent with previous studies[5, 7]
Summary
Acute myocardial infarction (AMI) is a serious ischemic heart disease with significant morbidity and mortality worldwide[1]. In the clinical setting and experimental studies of acute myocardial infarction (AMI), the most common alteration in TH metabolism is a decrease in T3 levels. This occurs during the early stage of AMI and is associated with an increased incidence of adverse cardiac events[10]. Animal studies have confirmed that short-term moderate supplementation with T3 can reduce myocyte apoptosis and improve cardiac function after MI[5, 11], which indicates that T3 treatment could serve as a potential therapeutic approach for protecting against MI. The optimal treatment duration of T3 is still worth exploring Severe cardiovascular diseases, such as myocardial infarction or heart failure, can alter thyroid hormone (TH) secretion and peripheral conversion, leading to low triiodothyronine (T3) syndrome. 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
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