An oxygen-sensing signal cascade of cardiomyocyte adaptations to moderate endurance training

Background and Puepose: The molecular pathological markers of vascular endothelial growth factor (VEGF), hypoxia inducible factor-1 alpha (HIF-1α), von Hippel-Lindau tumor suppressor protein (VHL) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC- 1α), are recently linked in the regulation of oxygen availability. The purpose of this study was to investigate these molecular markers of the cardiomyocyte adapt to moderate endurance training. Materials and Methods: we performed immunohistochemical staining coupled with image analysis for quantification in male Sprague- Dawley rat myocardium that had been trained on treadmill running at 20 m/min for 30 min on a 0% grade, for 3 days/wk. for 4 weeks (4WT) or 8 weeks (8WT) and control rats for 4 weeks (4WC) or 8 weeks (8WC) (n=6, respectively). Results: Training led to no significant alteration in HIF-1α content. Interestingly, a lower VHL content and higher VEGF contents were detected in the trained groups compared with their control counterparts (p<0.05). Additionally, PGC-1α showed higher content in the 8WT group than those in the 8WC and 4WT groups (p< 0.05), but no significant difference in PGC-1α content was found between the 4WT and 4WC groups. Conclusions: Downregulation of VHL in response to training may be the initiator responsible for activating the cardiomyocyte oxygen available for signaling cascades. Additionally, in the cardiomyocyte, moderate training-induced adaptation may occur faster in VEG- regulated oxygen availability than in the PGC-1α.