Ribonuclease 1 attenuates septic cardiomyopathy and cardiac apoptosis in a murine model of polymicrobial sepsis.
Anesthesiology
Immunology
Inflammation
Innate immunity
Pharmacology
Journal
JCI insight
ISSN: 2379-3708
Titre abrégé: JCI Insight
Pays: United States
ID NLM: 101676073
Informations de publication
Date de publication:
23 04 2020
23 04 2020
Historique:
received:
08
07
2019
accepted:
12
03
2020
pubmed:
28
3
2020
medline:
18
5
2021
entrez:
28
3
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 32213712
pii: 131571
doi: 10.1172/jci.insight.131571
pmc: PMC7205433
doi:
pii:
Substances chimiques
Carrier Proteins
0
Cell-Free Nucleic Acids
0
Proteins
0
RNH1 protein, human
0
ribonuclease inhibitor protein, mouse
0
Ribonuclease, Pancreatic
EC 3.1.27.5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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