Abstract
BackgroundSepsis-induced cardiomyopathy (SIC) is a common severe complication of sepsis that contributes to mortality. SIC is closely associated with excessive inflammatory responses, failed inflammation resolution, and apoptotic damage. Resolvin E1 (RvE1), an omega-3 polyunsaturated fatty acid (PUFA)-derived metabolite, has been reported to exert anti-inflammatory or proresolving activity in multiple animal models of inflammatory disease. However, the therapeutic potential of RvE1 in SIC remains undetermined, which was, therefore, the aim of the present study.MethodsC57BL/6J mice were randomly divided into three groups: control, lipopolysaccharide (LPS), and LPS + RvE1. Echocardiography, Western blotting (WB), quantitative real-time (QRT)-PCR, histological analyses, and flow cytometry were used to evaluate cardiac function, myocardial inflammation, and the underlying mechanisms.ResultsThe RvE1-injected group showed improved left ventricular (LV) function and reduced serum lactate dehydrogenase (LDH) and creatine kinase myocardial bound (CK-MB) levels. Compared to LPS treatment alone, RvE1 treatment inhibited the infiltration of neutrophils and macrophages into the heart and spleen and suppressed the secretion of pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and monocyte chemoattractant protein (MCP)-1, in the heart. We also observed that the activation of the mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB signaling pathways was blocked by RvE1 treatment, and this inhibition contributed to the improvement in the inflammatory response induced by LPS. RvE1 inhibited LPS-induced M1 macrophage polarization and promoted macrophage polarization toward the M2-like phenotype in both the heart and spleen. In addition, LPS administration dysregulated cyclooxygenase (COX) and lipoxygenase (LOX) in the heart, which were rectified by RvE1 treatment. RvE1 also reduced myocardial apoptosis rate in response to LPS-induced heart injury.ConclusionRvE1 protects the heart against SIC possibly through the inhibition of the MAPK and NF-κB inflammatory signaling pathways, modulation of macrophage polarization, and reduction in myocardial apoptosis. RvE1 may be a novel lipid mediator for the treatment of SIC.
Highlights
Sepsis is defined as life-threatening organ dysfunction and is caused by a dysregulated host response to infection
Whereas LV end-diastolic diameter (LVEDD) (Figure 2A) and LV end-systolic diameter (LVESD) (Figure 2B) were reversed by Resolvin E1 (RvE1) (25 μg/kg) treatment (Figures 2A–D), obviously increased, which suggest that LPS treatment reduces which indicates that RvE1 protects left ventricular (LV) function in LPSLV function
To test the effect of RvE1 on LPS-induced myocardial injury, we examined the levels of marker enzymes of myocardial injury in the serum
Summary
Sepsis is defined as life-threatening organ dysfunction and is caused by a dysregulated host response to infection. Sepsis-induced cardiomyopathy is a common complication of severe sepsis and is closely associated with the prognosis of patients. Evidence has suggested that myocardial injury caused by sepsis has characteristics of an excessive inflammatory response, failed resolution of inflammation, and apoptotic damage, which may bring about qualitative and quantitative myocardial alterations (Sharma, 2007; Deutschman and Tracey, 2014; Kong et al, 2017). It is imperative that a novel strategy to protect patients against sepsis-induced myocardial injury via the inhibition of inflammation, promotion of inflammation resolution, or inhibition of cardiac myocyte apoptosis is found. Sepsis-induced cardiomyopathy (SIC) is a common severe complication of sepsis that contributes to mortality. SIC is closely associated with excessive inflammatory responses, failed inflammation resolution, and apoptotic damage. The therapeutic potential of RvE1 in SIC remains undetermined, which was, the aim of the present study
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