Loss of MD1 exacerbates myocardial ischemia/reperfusion injury and susceptibility to ventricular arrhythmia.

Abstract

Myeloid differentiation protein 1(MD1), also known as lymphocyte antigen 86 (LY86), plays an important role in the toll-like receptor 4 (TLR4) signaling pathway. Recent studies show that MD1 is involved in regulating pressure overload-induced cardiac structural and electrical remodeling. However, the effect of MD1 on myocardial ischemia-reperfusion (I/R) injury and I/R related arrhythmia remains unknown. To further investigate that, the present study used MD1-knockout (MD1-KO) mice to study the role of MD1 in regulating myocardial I/R injury and its electrophysiology. The results demonstrate that the loss of MD1 led to a larger infarct size, increased activity of cardiac injury markers, aggravated histological damage, worsened cardiac function and decreased survival rate after myocardial I/R. Meanwhile, MD1 deficiency also aggravated inflammatory responses, promoted cardiomyocyte apoptosis and increased susceptibility to ventricular arrhythmia in mice subjected to myocardial I/R. Furthermore, loss of MD1 enhanced the activation of toll-like receptor 4 (TLR4) / nuclear factor kappa B (NF-κB) signaling pathway after myocardial I/R. Therefore, loss of MD1 exacerbated myocardial I/R injury and increased the susceptibility to ventricular arrhythmia, both of which are possibly related to the up-regulation of TLR4/NF-κB signaling pathway.

• Authors: Xiaobo Jiang, Bin Kong, Wei Shuai, Caijie Shen, Fan Yang, Hui Fu, He Huang
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 844 Pg. 79-86 (Feb 05 2019) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 30458167 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical References

• Antigens, Surface
• Ly86 protein, mouse
• Membrane Glycoproteins
• NF-kappa B
• Tlr4 protein, mouse
• Toll-Like Receptor 4

Topics

• Animals
• Antigens, Surface (genetics)
• Arrhythmias, Cardiac (genetics, metabolism, pathology, physiopathology)
• Heart (physiopathology)
• Male
• Membrane Glycoproteins (genetics)
• Mice, Knockout
• Myocardial Reperfusion Injury (genetics, metabolism, pathology, physiopathology)
• Myocardium (metabolism, pathology)
• NF-kappa B (metabolism)
• Toll-Like Receptor 4 (metabolism)