On November 6, Prof. Chen Chan, Prof. Zhu Tao, and Prof. Liu Jin of the Department of Anesthesiology of WCH published a research paper entitled Poly(I:C) Preconditioning Protects the Heart against Myocardial Ischemia/reperfusion Injury through TLR3/PI3K/Akt-dependent Pathway online in the famous international medical journal Signal Transduction and Targeted Therapy (IF: 13.493).
Myocardial ischemia/reperfusion injury is an important cause of heart failure after myocardial infarction, and effective prevention and treatment are needed. In this study, a synthetic double-stranded ribonucleic acid (dsRNA), the polyinosinic-polycytidylic acid (poly(I:C)) was used to pre-treat the mice myocardial ischemia/reperfusion model for the first time. Through evaluating the myocardial infarct size and the cardiac ultrasound function, we have found that poly(I:C) preconditioning could relieve myocardial ischemia/reperfusion injury. Meanwhile, TLR3 knockout mice, TLR3-FLAG plasmid transfection, and Akt-siRNA were used to confirm that the poly(I:C) preconditioning could improve cardiomyocytes tolerance of ischemia/reperfusion injury by activating the specific innate immune receptor TLR3 and its downstream PI3K/Akt signaling pathway, and regulating cell apoptosis and NF-κB related pro-inflammatory response. Also, the protein interaction between TLR3 and p85 PI3K was confirmed in myocardial tissue samples following ischemia/reperfusion injury by proximity ligation assay (PLA) and co-immunoprecipitation (IP) for the first time. Based on its unique antiviral and immunomodulatory effects, poly(I:C) is mainly applied in the viral infectious diseases and tumor adjuvant therapy.
This study will help expand the clinical application of poly (I: C), providing new targets for immune intervention in preventing myocardial ischemia/-reperfusion injury and improving myocardial infarction prognosis during the perioperative period.