Background: Caveolin-3 (Cav3) has been reported to protect both normal and failing hearts against myocardial ischemia/reperfusion (I/R) injury in rodent models. However, there is currently no evidence demonstrating its cardioprotective effects in human hearts. In this study, we investigate whether Cav3 is involved in myocardial I/R injury during cardiac surgery and the underlying mechanisms.
Methods: Human atrial tissues were collected from cardiac surgery patients before myocardial ischemia and 30 min after reperfusion. The tissue samples were analyzed by western blot to assess the expression levels of Cav3, pro-survival kinases, and apoptosis-related proteins. Immunofluorescence assessed Cav3 distribution, and apoptosis staining evaluated cardiomyocyte death. Cardiac enzymes, lactate levels, and hospitalization data were also recorded.
Results: The expression levels of cardiac Cav3 protein exhibit around 60% reduction following myocardial I/R injury in the human heart. The reduction of Cav3 showed a strong negative correlation with cardiac injury. Similarly, the phosphorylation of ERK1/2, Akt, STAT3, and GSK3β, is markedly downregulated in cardiac tissue following I/R injury. Furthermore, the pro-apoptotic protein Bax and caspase-3 shows substantial upregulation, while the anti-apoptotic protein Bcl-2 is significantly downregulated. Importantly, a strong positive correlation was observed between decreased Cav3 expression and reduced phosphorylation of survival kinases, while a negative correlation was found with cardiomyocyte apoptosis.
Conclusion: Our data suggest that the downregulation of Cav3 is associated with increased cardiac injury in the human heart. Targeting Cav3 may represent a promising therapeutic strategy for mitigating myocardial I/R injury in patients undergoing cardiac surgery.
Keywords: Cardiac surgery; Cardioprotection; Cardiopulmonary bypass; Caveolin-3; Ischemia/reperfusion injury.
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