Temporal changes in Krüppel-like factor 2 and thrombomodulin correlate with coagulation, endothelial, and liver damage in exertional heat stroke rats.

The Krüppel-like Factor 2 (KLF2) -Thrombomodulin (TM) axis is crucial for maintaining vascular homeostasis and coagulation balance. This study investigated its dynamic role and temporal characteristics in the development of coagulopathy following exertional heat stroke (EHS). Using a well-established rat model of EHS induced by strenuous exercise under high-temperature and high-humidity conditions, we conducted a detailed time-course analysis. Our findings revealed that plasma levels of KLF2 and TM underwent significant dynamic fluctuations following EHS induction. These alterations showed a clear correlation with progressive prolongations in standard coagulation parameters, specifically activated partial thromboplastin time (APTT) and prothrombin time (PT). The most profound disturbances in both the KLF2-TM axis and coagulation function were consistently observed at 4 h post-EHS. Notably, this critical time point was also associated with the peak severity of hepatic injury, as comprehensively assessed through histopathological examination and confirmatory liver function tests. Further analysis demonstrated that the aberrant expression of the KLF2-TM pathway within the liver tissue exhibited a distinct temporal consistency with the observed progression of hepatic pathological damage. Collectively, these results indicated that the KLF2-TM axis was actively involved in the pathogenic mechanisms underlying EHS-associated coagulopathy. Monitoring the dynamic changes of this axis may provide valuable predictive insights into the dysregulation of coagulation during EHS, suggesting its potential as a biomarker for disease severity.