Abstract
Septic cardiomyopathy is a life-threatening organ dysfunction caused by sepsis. Ribonuclease 1 (RNase 1) belongs to a group of host-defense peptides that specifically cleave extracellular RNA (eRNA). The activity of RNase 1 is inhibited by ribonuclease-inhibitor 1 (RNH1). However, the role of RNase 1 in septic cardiomyopathy and associated cardiac apoptosis is completely unknown. Here, we show that sepsis resulted in a significant increase in RNH1 and eRNA serum levels compared with those of healthy subjects. Treatment with RNase 1 resulted in a significant decrease of apoptosis, induced by the intrinsic pathway, and TNF expression in murine cardiomyocytes exposed to either necrotic cardiomyocytes or serum of septic patients for 16 hours. Additionally, treatment of septic mice with RNase 1 resulted in a reduction in cardiac apoptosis, TNF expression, and septic cardiomyopathy. These data demonstrate that eRNA plays a crucial role in the pathophysiology of the organ (cardiac) dysfunction in sepsis and that RNase and RNH1 may be new therapeutic targets and/or strategies to reduce the cardiac injury and dysfunction caused by sepsis.
Highlights
Sepsis is one of the most common causes of death on intensive care units (ICUs) and is defined as a life-threatening organ dysfunction secondary to an infection [1, 2]
After demonstrating that the exposure of murine cardiomyocytes in the presence of Ribonuclease 1 (RNase 1) resulted in reduced apoptosis, we investigated the effect of RNase 1 on cardiac function and cardiac apoptosis in a murine model of polymicrobial sepsis
Septic cardiomyopathy is a life-threatening organ dysfunction associated with a complicated postoperative course and increased mortality
Summary
Sepsis is one of the most common causes of death on intensive care units (ICUs) and is defined as a life-threatening organ dysfunction secondary to an infection [1, 2]. ERNA is released as a result of tissue injury and necrotic cell death from a variety of cells, including cardiomyocytes [9], and may play a role in differentiation, chromatin modification, and inflammation as well as tissue injury and repair [10,11,12,13,14]. It is unknown whether eRNA plays a role in septic cardiomyopathy and cardiac apoptosis. Playing a decisive role in septic cardiomyopathy [15], apoptosis represents a programmed, caspase-mediated cell death that is triggered by intrinsic or extrinsic signaling pathways
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