Role of KLF5 in Ischemia Reperfusion Injury
Acute myocardial infarction remains a leading cause of morbidity and mortality worldwide. Our previous studies have investigated the role of the transcription factor Kruppel-like factor 5 (KLF5) in various cardiac disease models, including diabetic cardiomyopathy and ischemic heart failure, and have linked it to the regulation of cellular stress responses, particularly those associated with oxidative stress and metabolic dysregulation. This study examines the role of KLF5 in exacerbating myocardial ischemia/reperfusion (I/R) injury and explores the potential cardioprotective benefit of KLF5 inhibition. Using the surgical model of myocardial I/R injury in both pigs and mice, we observed that KLF5 expression is upregulated in cardiomyocytes during early reperfusion. This increase in KLF5 expression is accompanied by enhanced oxidative stress, apoptosis, fibrosis, and adverse cardiac remodeling. Pharmacologic and cardiomyocyte-specific genetic inhibition of KLF5 significantly reduced infarct size, oxidative stress, and cell apoptosis markers, while preserving cardiac function over both acute and long-term reperfusion periods.To further explore the molecular pathways regulated by KLF5, bulk RNA sequencing was performed on myocardial tissue obtained from three groups of C57BL/6J mice: sham-operated wild-type mice, I/R-operated wild-type mice, and I/R-operated mice with pharmacological inhibition of KLF5 with ML264. By comparing the transcriptomic profiles across these groups, this study provides valuable insight into the gene regulatory networks affected by KLF5 during reperfusion and elucidates the molecular pathways through which KLF5 promotes myocardial I/R injury.This dataset offers a comprehensive understanding of the role of KLF5 in exacerbating I/R injury and supports the potential of KLF5 inhibition as a cardioprotective strategy against myocardial I/R injury.