Overexpression of miR-451a in sepsis and septic shock patients is involved in the regulation of sepsis-associated cardiac dysfunction and inflammation

Heng Wang,Guoxin Hu,Wenjuan Cui,Lujun Qiao

doi:10.1590/1678-4685-gmb-2020-0009

Abstract

The purpose of this study was to investigate the expression and clinical value of microRNA-451a (miR-451a) in septic patients and analyze its effect on sepsis-associated cardiac dysfunction and inflammation response. A rat model of sepsis was constructed by cecal ligation and puncture. The expression of miR-451a was measured by quantitative real-time PCR. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic value of serum miR-451a. The cardiac function and inflammatory responses in septic rats were measured to explore the functional role of miR-451a. Serum expression of miR-451a was increased in septic patients compared with healthy controls, and had the ability to distinguish septic patients from healthy volunteers with a sensitivity and specificity of 87.8% and 81.5%, respectively. Elevated serum miR-451a was associated with sepsis severity, as evidenced by the increased expression of miR-451a in septic shock patients and its correlation with key clinical indicators. Significantly upregulated expression of miR-451a was found in septic patients with cardiac dysfunction, and the knockdown of miR-451a in sepsis rats improved cardiac function and inhibited inflammatory responses. All the data revealed that serum miR-451a serves as a candidate diagnostic biomarker of sepsis and a potential parameter to indicate disease severity. The reduction of miR-451a may mitigate sepsis-induced cardiac dysfunction and inflammatory responses.

Highlights

Sepsis is a systemic inflammatory response syndrome resulting from infection and a leading cause of multiple organ failure and even death (Napolitano, 2018)
The results indicated that there were no differences in age, gender and BMI between the septic patients and healthy controls
This study evaluated the APACHE II score and SOFA score to determine the severity of sepsis in patients, and the APACHE II score was 11.57 ± 2.66 and SOFA score was 5.60 ± 1.55

Summary

Introduction

Sepsis is a systemic inflammatory response syndrome resulting from infection and a leading cause of multiple organ failure and even death (Napolitano, 2018). The pathogenesis of sepsis is characterized by uncontrolled inflammatory responses and immune dysfunction (Rello et al, 2017). Progress has been made in the treatment and life support for this condition, the mortality of sepsis remains high especially in intensive care units (ICU) (Verdonk et al, 2017). Cardiac dysfunction is considered to be a frequent complication of severe sepsis, and is responsible for the deaths occurred in sepsis patients in ICU (Zheng et al, 2017). In addition to antibiotics treatments and symptomatic therapeutic methods, such as restoration of blood pressure and systemic perfusion, the strategies to reduce cardiac dysfunction have received increasing attention (Lv and Wang, 2016)

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