Levosimendan Protects Cardiomyocytes from Sepsis-Induced Inflammation, Endoplasmic Reticulum Stress, and Cell Death

Yuxiao Liu, Liangming Zhuang, Chao Chen, Xinxin Qi, Siting Ye, Zhongmin Gu

Article ID: 7111
Vol 37, Issue 1, 2023
DOI: https://doi.org/10.23812/j.biol.regul.homeost.agents.20233701.58
Received: 8 February 2023; Accepted: 8 February 2023; Available online: 8 February 2023; Issue release: 8 February 2023

Abstract

Introduction: Sepsis-induced cardiomyopathy is one of the main causes of death in critical patients worldwide. Levosimendan is a diastolic agent with a clinical use in patients with acute decompensated chronic heart failure. In this study, we aimed to explore the molecular mechanism of levosimendan in the treatment of septic cardiomyopathy. Methods: Rat cardiomyocytes H9c2 cells were treated with lipopolysaccharide (LPS) and levosimendan for 24 h or were intraperitoneally injected into rats for 12 or 14 h. Cell survival and apoptosis were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide and flow cytometry. The secretion levels of inflammatory factors (interleukin-1β, interleukin-18, MCP-1 (monocyte chemoattractant protein-1)) and the expression levels of endoplasmic reticulum stress-related molecules were detected by enzyme-linked immunosorbent assay, western blotting and quantitative PCR (polymerase chain reaction). Hematoxylin-eosin staining was used to observe myocardial tissue lesions. Results: Levosimendan alleviated LPS-induced apoptosis, secretion of interleukin-1β, interleukin-18, MCP-1 and expression levels of caspase 12, IRE1 (inositol-requiring enzyme 1) and GRP78 (a glucose regulatory protein with a molecular weight of 78 ku), relieved the inhibition of LPS on cell viability and SIRT7 (silencing regulatory protein 7) expression, and attenuated myocardial damage caused by LPS. Conclusions: Levosimendan inhibited inflammation and ER (endoplasmic reticulum stress), and thus rescued LPS induced septic cardiac insufficiency in rats.


Keywords

levosimendan;lipopolysaccharide;septic cardiac insufficiency;inflammatory cytokines;endoplasmic reticulum stress


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