Protective Effect of Trimetazidine on Potassium Ion Homeostasis in Myocardial Tissue in Mice with Heart Failure.

Kaijing Yang,Linlin Song,Yan Li,Yitao Xue,Huachen Jiao,Nannan Chen,Yang Sun,Kaiming Chen,Dadong Guo,Ting Yu,Xijin Wei,Wenwen Liu,Miao Yu,Zhizhong Song

doi:10.1155/2022/2387860

Abstract

The occurrence of heart failure (HF) is closely correlated with the disturbance of mitochondrial energy metabolism, and trimetazidine (TMZ) has been regarded as an effective agent in treating HF. Intracellular potassium ion (K+) homeostasis, which is modulated by K+ channels and transporters, is crucial for maintaining normal myocardial function and can be disrupted by HF. This study is aimed at exploring the protective effect of TMZ on K+ homeostasis within myocardial tissue in mice with HF. We observed the pathological changes of myocardial tissue under microscopes and further measured the content of adenosine triphosphate (ATP), the activity of Na+-K+ ATPase, and the expression of ATP1α1 at the mRNA and protein levels. Moreover, we also analyzed the changes in K+ flux across the myocardial tissue in mice. As a result, we found that there was a large amount of myocardial fiber lysis and fracture in HF myocardial tissue. Meanwhile, the potassium flux of mice with HF was reduced, and the expression of ATP1α1, the activity of Na+-K+ ATPase, and the supply and delivery of ATP were also decreased. In contrast, TMZ can effectively treat HF by restoring K+ homeostasis in the local microenvironment of myocardial tissues.

Highlights

Heart failure (HF) is defined as a complex clinical syndrome in which ventricular filling or ejection function is damaged due to various organic or functional heart diseases, accompanied by reduced cardiac output
After TMZ treatment, we noted that the EF of the mice in the TMZ group was apparently restored compared with that of the MOD group (60:34 ± 4% vs. 51:36 ± 3%, ##P < 0:01, Figure 1), indicating the good therapeutic effect of TMZ on HF
The comparison of brain natriuretic peptide (BNP) levels in serum between the MOD and normal control (NC) groups showed that the BNP level in the MOD group was significantly higher than that in the NC group, and the difference was statistically significant (Table 2, ∗∗∗P < 0:001), indicating that the HF model of mice was successfully established

Summary

Introduction

Heart failure (HF) is defined as a complex clinical syndrome in which ventricular filling or ejection function is damaged due to various organic or functional heart diseases, accompanied by reduced cardiac output. HF is the main cause of death from cardiovascular diseases and seriously threatens human life and health, affecting approximately 23 million patients worldwide [1, 2]. The heart produces myocardial energy through the oxidation of glucose and fatty acids, thereby regulating heart function and efficiency [4]. In HF, the oxidative metabolism of mitochondria is impaired, and the oxidation of mitochondrial fatty acids exceeds the oxidation of mitochondrial glucose, causing pyruvate to accumulate and convert into lactic acid, further accelerating cell apoptosis [5, 6]. Trimetazidine (TMZ) is a fatty acid oxidation inhibitor that inhibits 3ketoacyl CoA thiolase, and it can enhance glucose oxidation

Objectives

Methods

Results

Discussion

Conclusion