Predictive value and regulatory mechanism of serum miR-499a-5p on myocardial dysfunction in sepsis

Chuang Yang,Kun Wen

doi:10.1186/s13019-021-01679-5

Abstract

BackgroundThis study sought to investigate the predictive value and regulatory mechanism of serum miR-499a-5p in sepsis-induced myocardial dysfunction (SIMD).MethodsA total of 60 patients with sepsis and 60 healthy volunteers were enrolled in this study. The serum levels of miRNAs (miR-451, miR-378 and miR-499a-5p) were detected. Receiver operating characteristic curve and logistic regression analysis were used to evaluate the diagnostic and prognostic value of miR-499a-5p in SIMD patients. AC16 cells were used to establish SIMD model in vitro using lipopolysaccharide (LPS). An analysis was conducted for miR-499a-5p expression, cell viability, and the concentration of creatine kinase-MB isoform (CK-MB), brain natriuretic peptide (BNP), superoxide dismutase (SOD) and cytochrome C oxidase IV (COX IV). The downstream target of miR-499a-5p was verified.ResultsOur results revealed a poor expression of miR-499a-5p in the serum of SIMD patients, while no significant difference was evident for miR-451 and miR-378. The level of miR-499a-5p in the survival group was higher than the non-survival group. miR-499a-5p elicited good diagnostic and prognostic value for SIMD. Our findings revealed that miR-499a-5p was decreased significantly in LPS-treated cardiomyocytes. After overexpression of miR-499a-5p, the cell viability increased, and the concentrations of CK-MB and BNP were decreased, while the concentrations of SOD and COX IV were increased. EIF4E was validated as the target of miR-499a-5p. After overexpression of EIF4E, the cell viability was decreased and the concentrations of CK-MB and BNP were increased while the concentrations of SOD and COX IV were decreased.ConclusionThe level of miR-499a-5p is weak in SIMD patients. miR-499a-5p has a good diagnostic and prognostic value for SIMD by inhibiting EIF4E transcription.

Highlights

Sepsis is a systemic syndrome induced by an immediate response to infection or injury [1, 2]
No significant difference was evident in parameters such as age, gender and body mass index (BMI) between healthy subjects and sepsis patients (P > 0.05), the serum PCT, C-reactive protein (CRP) and brain natriuretic peptide (BNP) levels in sepsis-induced myocardial dysfunction (SIMD) patients were higher than those in healthy participants (P < 0.05)
BMI, body mass index; CRP, C-reactive protein; PCT, procalcitoninl; BNP, Brain Natriuretic Peptide with myocardial diseases according to the miRNAs predicted in a previous study [23]

Summary

Introduction

Sepsis is a systemic syndrome induced by an immediate response to infection or injury [1, 2]. Sepsis is synonymous with high morbidity and mortality around the globe and poses an increasing burden on patients of. Yang and Wen J Cardiothorac Surg (2021) 16:301 function of lung, kidney and cardiovascular system [6]. Subsequent complicated intra-myocardial inflammation in sepsis could induce myocardial dysfunction [7]. Myocardial dysfunction is a prevalent complication of sepsis responsible for increased mortality in sepsis [8]. The current incidence of sepsis-induced cardiomyopathy is about 50% with 70% mortality [9]. Currently no specific drug treatment could reverse the sepsis-induced myocardial dysfunction (SIMD). This study sought to investigate the predictive value and regulatory mechanism of serum miR-499a-5p in sepsis-induced myocardial dysfunction (SIMD)

Methods

Results

Discussion

Conclusion