2. Academic Validation
  3. Poly(I:C) preconditioning protects the heart against myocardial ischemia/reperfusion injury through TLR3/PI3K/Akt-dependent pathway

Poly(I:C) preconditioning protects the heart against myocardial ischemia/reperfusion injury through TLR3/PI3K/Akt-dependent pathway

  • Signal Transduct Target Ther. 2020 Nov 6;5(1):216. doi: 10.1038/s41392-020-00257-w.
Erya Chen 1,  Chan Chen 2,  Zhendong Niu 3,  Lu Gan 1,  Qiao Wang 1,  Ming Li 1,  XingWei Cai 1,  Rui Gao 1,  Sruthi Katakam 4,  Hai Chen 1,  Shu Zhang 3,  Ronghua Zhou 1,  Xu Cheng 1,  Yanhua Qiu 1,  Hai Yu 1,  Tao Zhu 5,  Jin Liu 6
Affiliations

Affiliations

  • 1 Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • 2 Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China. [email protected].
  • 3 Department of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
  • 4 Institute of Cell Engineering, Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • 5 Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China. [email protected].
  • 6 Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China. [email protected].
PMID: 33154351 DOI: 10.1038/s41392-020-00257-w
Abstract

Emerging evidence suggests that Toll-like receptors (TLRs) ligands pretreatment may play a vital role in the progress of myocardial ischemia/reperfusion (I/R) injury. As the ligand of TLR3, polyinosinic-polycytidylic acid (poly(I:C)), a synthetic double-stranded RNA, whether its preconditioning can exhibit a cardioprotective phenotype remains unknown. Here, we report the protective effect of poly(I:C) pretreatment in acute myocardial I/R injury by activating TLR3/PI3K/Akt signaling pathway. Poly(I:C) pretreatment leads to a significant reduction of infarct size, improvement of cardiac function, and downregulation of inflammatory cytokines and apoptotic molecules compared with controls. Subsequently, our data demonstrate that phosphorylation of TLR3 tyrosine residue and its interaction with PI3K is enhanced, and protein levels of phospho-PI3K and phospho-Akt are both increased after poly(I:C) pretreatment, while knock out of TLR3 suppresses the cardioprotection of poly(I:C) preconditioning through a decreased activation of PI3K/Akt signaling. Moreover, inhibition of p85 PI3K by the administration of LY294002 in vivo and knockdown of Akt by siRNA in vitro significantly abolish poly(I:C) preconditioning-induced cardioprotective effect. In conclusion, our results reveal that poly(I:C) preconditioning exhibits essential protection in myocardial I/R injury via its modulation of TLR3, and the downstream PI3K/Akt signaling, which may provide a potential pharmacologic target for perioperative cardioprotection.

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