The transcription factor interferon regulatory factor‐1 is an endogenous mediator of myocardial ischemia reperfusion injury

Abstract

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. In the current study, microarray data indicated that IRF1 expression was consistently changed in the 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 (iNOS), and augmented oxidative stress. Taken together, 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.

Interferon‐regulatory factor‐1 boosts bevacizumab cardiotoxicity by the vascular endothelial growth factor A/14‐3‐3γ axis

“…Recent studies have identified IRF1 as a transcription factor regulating the occurrence and development of cardiovascular diseases 11 . In addition, IRF1 is an important endogenous mediator of ischaemic cardiomyopathy, with evidence suggesting that IRF1 overexpression could promote myocardial ischaemia–reperfusion injury 12,13 . Furthermore, IRF1 has been found to inhibit proliferation and exert a pro‐apoptotic effect in hepatocellular carcinoma cells 14 .…”

“… 11 In addition, IRF1 is an important endogenous mediator of ischaemic cardiomyopathy, with evidence suggesting that IRF1 overexpression could promote myocardial ischaemia–reperfusion injury. 12 , 13 Furthermore, IRF1 has been found to inhibit proliferation and exert a pro‐apoptotic effect in hepatocellular carcinoma cells. 14 A previous study found that IRF1 overexpression decreased VEGFA protein levels and suppressed osteosarcoma progression.…”