Ribonuclease 1 attenuates septic cardiomyopathy and cardiac apoptosis in a murine model of polymicrobial sepsis
Open Access
- 23 April 2020
- journal article
- research article
- Published by American Society for Clinical Investigation in JCI Insight
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.Funding Information
- START (113/17)
- Deutsche Forschungsgemeinschaft (MA 7082/1-1)
- Bundesministerium für Bildung und Forschung (03Z22JN12)
This publication has 51 references indexed in Scilit:
- Role of Extracellular RNA and TLR3‐Trif Signaling in Myocardial Ischemia–Reperfusion InjuryJournal of the American Heart Association, 2014
- Alarmins: awaiting a clinical responseJCI Insight, 2012
- MicroRNAs bind to Toll-like receptors to induce prometastatic inflammatory responseProceedings of the National Academy of Sciences of the United States of America, 2012
- Cardiomyocyte Microvesicles Contain DNA/RNA and Convey Biological Messages to Target CellsPLOS ONE, 2012
- MiRNA in innate immune responses: novel players in wound inflammationPhysiological Genomics, 2011
- Apoptosis in Cardiovascular Diseases: Mechanism and Clinical ImplicationsKorean Circulation Journal, 2010
- Degradation by Stratum Corneum Proteases Prevents Endogenous RNase Inhibitor from Blocking Antimicrobial Activities of RNase 5 and RNase 7Journal of Investigative Dermatology, 2009
- Extracellular RNA constitutes a natural procoagulant cofactor in blood coagulationProceedings of the National Academy of Sciences of the United States of America, 2007
- Tumor necrosis factor alpha-induced apoptosis in cardiac myocytes. Involvement of the sphingolipid signaling cascade in cardiac cell death.JCI Insight, 1996
- Extracellular ‘communicator RNA’FEBS Letters, 1988