The Transcription Factor Interferon Regulatory Factor-1 Is An Endogenous Mediator Of Myocardial Ischemia Reperfusion Injury

Objectives: Myocardial ischemia reperfusion(MIR)injury negatively affects the prognosis of acute myocardial infarction(AMI),while effective suppression of MIR injury remains a largely unmet clinical need.Interferon regulatory factors(IRF)are key players in chronic cardiac disorders such as cardiac remodeling.However,their roles in acute MIR injury remain largely unknown.This study aimed to determine the roles of IRF1 in ischemia/reperfusion-induced myocardial injury and to investigate the underlying mechanisms involved.Methods and Results: In current study,microarray data indicated that IRF1 expression was significantly changed in both human ischemic heart and ischemic reperfused mouse heart.Western blot analysis confirmed the expression alterations of IRF1 in ischemic reperfused mouse heart.Cardiac-specific IRF1 knockdown significantly decreased infarct size,improved cardiac function,and suppressed myocardial apoptosis after MIR injury.Conversely,cardiac-specific IRF1 overexpression significantly promoted MIR injury.Further investigation revealed that IRF1 transcriptionally regulated the expression of inducible nitric oxide synthase(i NOS),and augmented oxidative stress.Conclusions: we presented the first direct evidence that IRF1 served as a mediator of MIR injury,and IRF1 may represent a potential therapeutic target for alleviating MIR injury.