The role of mitofilin in left ventricular hypertrophy in hemodialysis patients

Qi-Shun Wu,Qing He,Jian-Qiang He,Jun Chao,Wen-Yan Wang,Yan Zhou,Ji-Zhuang Lou,Wei Kong,Jun-Feng Chen

doi:10.1080/0886022x.2018.1456455

Abstract

Left ventricular hypertrophy (LVH) is a common abnormality in hemodialysis (HD) patients. Mitochondrial dysfunction contributes to the progression of LVH. As an inner mitochondrial membrane structural protein, mitofilin plays a key role in maintaining mitochondrial structure and function. The aim of this study was to investigate the relationship between mitofilin and LVH in HD patients. A total of 98 HD patients and 32 healthy controls were included in the study. Serum N-terminal proBNP (NT-proBNP), endothelin-1 (ET-1), and atrial natriuretic peptide (ANP) were examined. The protein level of mitofilin and the mitochondrial DNA (mtDNA) copy number were estimated in peripheral blood mononuclear cells (PBMCs). The left ventricle mass index (LVMI) was evaluated in all participants, and the interaction between these variables and the LVMI was assessed. The LVMI was positively correlated with the NT-proBNP, ET-1, and ANP levels, and it was negatively correlated with mtDNA copy number and mitofilin levels. Multiple regression analysis showed that the NT-proBNP, ET-1, and ANP levels as well as mitofilin levels and mtDNA copy number were associated with the LVMI. Although further research of these associations is needed, this result suggests that LVH may affect the levels of mitofilin in HD patients.

Highlights

Cardiovascular diseases (CVDs), including coronary artery disease, congestive heart failure, and sudden cardiac death, are the main cause of morbidity and mortality in hemodialysis (HD) patients
The two groups were homogenous in terms of age, gender, body mass index (BMI), urea reduction ratio (URR), kt/V, hemoglobin, blood platelet, C-reactive protein (CRP), Table 1
We demonstrated that mitofilin, a previously identified mitochondrial protein expressed in peripheral blood mononuclear cells (PBMCs), may be correlated with Left ventricular hypertrophy (LVH) in HD patients

Summary

Introduction

Cardiovascular diseases (CVDs), including coronary artery disease, congestive heart failure, and sudden cardiac death, are the main cause of morbidity and mortality in hemodialysis (HD) patients. Left ventricular hypertrophy (LVH) is a major cardiovascular risk factor that predicts mortality in HD patients [1,2]. Hypertension, diabetes, increased body mass index (BMI), gender, age, anemia, and hyperparathyroidism have been described as the risk factors for LVH [3]. Other risk factors may be involved in the pathophysiological process, and they must be investigated. A mitochondrial inner membrane protein that is highly expressed in the heart [6], plays a central role in maintaining cristae morphology and structure [7]. Experimental studies have shown that mitofilin is an important factor implicated in cell apoptosis, oxidative stress, and mitochondrial biogenesis [8–10]. Its impact on LVH in dialysis patients has been unclear until now

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