Exercise training before cardiac-specific Serca2 disruption attenuates the decline in cardiac function in mice

Area of Science:

• Cardiovascular Physiology
• Exercise Science
• Molecular Cardiology

Background:

• Sarco(endo)plasmic Ca(2+)-ATPase (SERCA2) is critical for cardiac contractility and function.
• Reduced SERCA2 is linked to impaired cardiac performance, while exercise training can enhance SERCA2 function.
• The study investigates if pre-emptive exercise training mitigates cardiac dysfunction following acute SERCA2 disruption.

Purpose of the Study:

• To determine if exercise training prior to cardiomyocyte-specific SERCA2 gene disruption delays the onset of cardiac dysfunction in mice.
• To assess the impact of exercise on cardiac function and aerobic capacity following SERCA2 knockout.

Main Methods:

• Mice underwent 6 weeks of high-intensity interval treadmill training before tamoxifen-induced Serca2 gene disruption.
• Cardiac function, maximal oxygen uptake (Vo(2max)), and cardiac output were measured in trained and sedentary SERCA2 knockout (S2KO) mice.
• Comparisons were made between trained S2KO mice and their sedentary counterparts post-gene disruption.

Main Results:

• Both trained and sedentary mice showed comparable improvements in Vo(2max), left ventricle weight, and running speed after training.
• Trained S2KO mice exhibited a slower decline in cardiac function and maintained higher Vo(2max) for 15 days post-Serca2 disruption compared to sedentary S2KO mice.
• Six weeks after Serca2 disruption, trained S2KO mice had higher cardiac output than sedentary S2KO mice.

Conclusions:

• Exercise training attenuates the decline in cardiac performance caused by acute SERCA2 gene disruption in the heart.
• These findings suggest that mechanisms independent of SERCA2 contribute to the cardioprotective effects of exercise training.
• Pre-emptive exercise may enhance cardiac resilience through pathways other than direct SERCA2 upregulation.