Introduction:
Mammalian hibernation is a natural molecular adaptation to extreme environmental conditions with important applications for perioperative organ protection. We conducted an integrated proteomic analysis to identify species and season-specific correlates of the cardioprotective phenotype.
Methods:
Quantitative 2D-LC/LC-MS/MS was used in the myocardium of summer active arctic ground squirrels (AGS), winter hibernating AGS, and rats subjected to deep hypothermic cardiac arrest and reperfusion.
Results:
Hibernating AGS display robust cardioprotection in our model of I/R compared with rats using both biomarker (Fig 1) and echocardiographic assessment of cardiac injury. Proteomic analysis revealed significant reduction in subunits of all five electron transport chain (ETC) complexes in hibernating AGS compared with rats, only complex 5 showed increased expression of some subunits after I/R.Fig 2
Conclusions:
Proteomic profiling revealed dichotomy in the cardioprotective adaptations employed by hibernating AGS and rat. The proteomic profile of hibernating AGS resembles that of myocardial hibernation in other mammals, with significant downregulation of mitochondrial ETC complexes. However, unlike myocardial hibernation in non-hibernators, AGS demonstrated downregulation of glycolytic and other myocardial energetic pathways with the exception of fatty acid oxidation. Sirtuin 3 - a key regulator of mitochondrial bioenergetics - was robustly upregulated in AGS, suggesting that preventing hyperacetylation of key metabolic enzymes may be a cardioprotective strategy employed by hibernators.
