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

Abstract

AIMS:

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. 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 METHODS:

Adult 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 FINDINGS:

Compared 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.

SIGNIFICANCE:

T3 pretreatment can protect the heart against dysfunction post-MI, which may be mediated by the activation of the IGF-1/PI3K/AKT signaling pathway.

• Authors: Bin Zeng, Xiaoting Liao, Lei Liu, Caixia Zhang, Huaiyu Ruan, Bo Yang
• Journal: Life sciences (Life Sci) Vol. 267 Pg. 118977 (Feb 15 2021) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 33383053 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Cardiotonic Agents
• Thyroid Hormones
• Triiodothyronine
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Apoptosis (drug effects)
• Atrial Remodeling (drug effects, physiology)
• Cardiotonic Agents (metabolism, pharmacology)
• Fibrosis
• Heart Failure (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Myocardial Infarction (drug therapy, pathology)
• Myocardium (metabolism)
• Myocytes, Cardiac (metabolism)
• Oxidative Stress (drug effects)
• Phosphatidylinositol 3-Kinases (metabolism)
• Phosphorylation
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction (drug effects)
• Thyroid Hormones (metabolism, physiology)
• Triiodothyronine (metabolism, pharmacology)
• Ventricular Function, Left (drug effects)