Impact of physical exercise on cardiac function and molecular pathways in mice with early HFpEF

Abstract Background Exercise intolerance and skeletal muscle dysfunction are hallmarks of heart failure (HF) progression. Cumulative evidence supports cardioprotective effects of exercise, although the molecular mechanisms mediating these cardiac benefits in HF with preserved ejection fraction (HFpEF) have not been fully elucidated. Aims To evaluate the effects of two different exercise programs (moderate and intense) on cardiac remodelling and function in a mouse model of early HFpEF induced by hypertension and high fat diet, along with the mitochondrial adaptations in skeletal muscle. Methods HFpEF was induced with L-NAME in drinking water combined with a high fat diet, followed by 8 weeks of either intense exercise program (5 sessions running in the treadmill per week), moderate exercise (3 sessions/week), or sedentary behaviour. Blood pressure was assessed by the tail-cuff method and cardiac function was assessed by echocardiography. Cardiac tissue was stained with wheat germ agglutinin to assess cardiomyocyte hypertrophy. Transcriptomic analysis of cardiac tissue was performed in cardiac samples. Skeletal muscle mitochondrial function was analysed using the Oroboros O2K system. Results HFpEF mice exhibited elevated systolic blood pressure (P