MicroRNA-495 serves as a diagnostic biomarker in patients with sepsis and regulates sepsis-induced inflammation and cardiac dysfunction

Abstract

Background: Sepsis leads to severe inflammatory and cardiac dysfunction. This study aimed to explore the clinical value of miR-495 in sepsis, as well as its role in sepsis-induced inflammation and cardiac dysfunction. Methods: 105 sepsis patients were recruited; receiver operating characteristic (ROC) curve was plotted to assess the diagnostic value of miR-495 in sepsis. A model of sepsis in rats was created via performing cecal ligation and puncture (CLP). After modeling, the cardiac function, including left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP) and maximum rate of rise/fall of left ventricle pressure (± dp/dt max), and serum cardiac troponin I (CTn-I), creative kinase isoenzyme MB (CK-MB) were detected. The blood cytokines levels including TNF-α, IL-6, IL-1β were also measured. Quantitative real-time PCR (qRT-PCR) was used for the measurement of the expression level of miR-495. Results: MiR-495 was significantly downregulated in sepsis patients, especially patients who suffered from septic shock (SS). MiR-495 expression was negatively associated with Scr, WBC, CRP, PCT, APACHE II score and SOFA score. MiR-495 could distinguish patients with SS from non-SS patients. MiR-495 and SOFA score were better indictors for the occurrence of cardiac dysfunction in sepsis patients. In CLP-induced sepsis model. CLP rats experienced deterioration of LVSP, LVEDP, ± dp/dt max , and had a rise in serum CTn-I, CK-MB, TNF-α, IL-6 and IL-1β, which were improved by miR-495 agomir injection. Conclusions: MiR-495 might be a potential diagnostic biomarker for sepsis patients, and overexpression of miR-495 alleviated sepsis-induced inflammation and cardiac dysfunction.

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

“…As previously described, rats were subjected to CLP to induce sepsis condition. Consistent with the previous study, cardiac function of rats was impaired after CLP (Guo et al, 2019). Moreover, after the knockdown of miR-451a, the impaired cardiac function in sepsis rats, which evidenced by serum cardiac function biomarkers and hemodynamic index, was significantly improved.…”

“…The abnormal expression of miRNAs has been reported to be involved in the regulation of inflammatory response in several human disease, including sepsis. For example, miR-495 has been identified to be downregulated in the serum of sepsis patients, and the in vitro study further confirmed that overexpression of miR-495 can alleviate CLP induced inflammatory response (Guo et al, 2019). In the present study, we found that the enhanced inflammatory response was remarkably reversed by the reduction of miR-451a in our constructed septic rat model, as shown by the decreases in pro-inflammatory cytokine levels.…”

Diagnostic Value of miR-103 in Patients with Sepsis and Noninfectious SIRS and Its Regulatory Role in LPS-Induced Inflammatory Response by Targeting TLR4

“…miRNAs can be easily detected from serum and plasma samples, making them a group of good diagnostic tools in various diseases [27]. Guo et al provided evidence for the decreased serum miR-495 as a diagnostic biomarker to screen sepsis patients from healthy population [28]. Lan et al reported that serum miR-155-5p and miR-133a-3p levels were increased in sepsis and related with disease severity, which served as candidate biomarkers for the diagnosis of sepsis [11].…”

MicroRNAs and Sepsis-Induced Cardiac Dysfunction: A Systematic Review

“…MiR-495 was found to be down-regulated in blood samples of septic patients by Guo et al [ 65 ]. Furthermore, it was more decreased in patients who developed septic shock.…”