KLF9 aggravates ischemic injury in cardiomyocytes through augmenting oxidative stress.

Cardiomyocyte injury caused by excessive oxidative stress underlies the pathogenesis of myocardial infarction (MI), a devastating disease leading to heart failure and death. The Krüppel-like factor 9 (KLF9) is a transcriptional factor that has recently been reported to regulate oxidative stress, however, whether it is associated with cardiomyocyte injury and MI is unknown. We found that KLF9 was upregulated in the heart from a rat MI model. In addition, KLF9 was also upregulated in cardiomyocytes exposed to ischemia in vitro, suggesting that KLF9 responds to MI-relevant stimuli. Moreover, KLF9 knockdown protected cardiomyocytes against ischemic injury. Mechanistically, KLF9 knockdown reduced reactive oxygen species (ROS) generation in ischemic cardiomyocytes through upregulating the antioxidant thioredoxin reductase 2 (Txnrd2), and more important, Txnrd2 silencing abrogated KLF9 knockdown-mediated cardioprotection in ischemic cardiomyocytes. Altogether, these results suggest that KLF9 aggravates ischemic injury in cardiomyocytes through undermining Txnrd2-mediated ROS clearance, which might offer KLF9 as a possible target in alleviating MI.