Abstract
The lungs are highly susceptible to injury, including ischemia/reperfusion (I/R) injury. Pulmonary I/R injury can occur when correcting conditions such as primary pulmonary hypertension, and is also relatively common after lung transplantation or other cardiothoracic surgery. Methods to reduce pulmonary I/R injury are urgently needed to improve outcomes following procedures such as lung transplantation. Remote liver ischemic preconditioning (RLIPC) is an effective cardioprotective measure, reducing damage caused by subsequent cardiac I/R injury, but little is known about its potential role in pulmonary protection. Here, we analyzed the efficacy and mechanistic basis of RLIPC in a rat model of pulmonary I/R injury. RLIPC reduced lung I/R injury, lessening structural damage, inflammatory cytokine production and apoptosis. In addition, RLIPC preserved pulmonary function compared to controls following lung I/R injury. RLIPC stimulated phosphorylation of pulmonary STAT3, a component of the SAFE signaling pathway, but not phosphorylation of RISK pathway signaling proteins. Accordingly, STAT3 inhibition using AG490 eliminated the pulmonary protection afforded by RLIPC. Our data demonstrate for the first time that RLIPC protects against pulmonary I/R injury, via a signaling pathway requiring STAT3 phosphorylation.
Highlights
Data Availability Statement: All relevant data are within the paper and its Supporting Information files
Remote liver ischemic preconditioning (RLIPC) is an effective cardioprotective measure, reducing damage caused by subsequent cardiac I/R injury, but little is known about its potential role in pulmonary protection
Rats were assigned to a sham-operated group (”Sham”, in which the hepatic arterial and venous trunk were exposed without intervention, and lung was exposed without ligation), control group (CON, no further hepatic intervention) or remote liver ischemic preconditioning group (RLIPC) group
Summary
Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Remote ischemic preconditioning refers to an intervention in which ischemia is induced in one organ or region of the body to induce a protective effect in another organ undergoing I/R injury. The question still remains whether this brief liver ischemia-induced preconditioning can raise the tolerance to reperfusion-induced lung injury, and if so, can we identify an underlying molecular mechanism that could be potentially be leveraged therapeutically in the future. We describe application of remote liver ischemic preconditioning (RLIPC) to a rat pulmonary I/R injury model, and report an underlying molecular mechanism for its protective effect
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