Endurance training restores spatially distinct cardiac mitochondrial function and myocardial contractility in ovariectomized rats

We previously demonstrated that the loss of female hormones induces cardiac and mitochondrial dysfunction in the female heart. Here, we show the impact of endurance training for twelve weeks, a nonpharmacological therapy against cardiovascular disease caused by ovariectomy and its contribution to cardiac contractility, mitochondrial quality control, bioenergetics and oxidative damage. We found that ovariectomy induced cardiac hypertrophy and dysfunction by decreasing SERCA2 and increasing phospholamban protein expression. Endurance training restored myocardial contractility, SERCA2 levels, increased calcium transient in ovariectomized rats but did not change phospholamban protein expression or cardiac hypertrophy. Additionally, ovariectomy decreased the amount of intermyofibrillar mitochondria and induced mitochondrial fragmentation that were accompanied by decreased levels of mitofusin 1, PGC-1α, NRF-1, total AMPK-α and mitochondrial Tfam. Endurance training prevented all these features except for mitofusin 1. Ovariectomy reduced O₂ consumption, elevated O₂ ^.- release and increased Ca²⁺-induced mitochondrial permeability transition pore opening in both mitochondrial subpopulations. Ovariectomy also increased NOX-4 protein expression in the heart, reduced mitochondrial Mn-SOD, catalase protein expression and increased protein carbonylation in both mitochondrial subpopulations, which were prevented by endurance training. Taken together, our findings show that endurance training prevented cardiac contractile dysfunction and mitochondrial quality control in ovariectomized rats.