Lipidomic Profiles of the Heart and Circulation in Response to Exercise versus Cardiac Pathology: A Resource of Potential Biomarkers and Drug Targets

Abstract

Summary: Exercise-induced heart growth provides protection against cardiovascular disease, whereas disease-induced heart growth leads to heart failure. These distinct forms of growth are associated with different molecular profiles (e.g., mRNAs, non-coding RNAs, and proteins), and targeting differentially regulated genes has therapeutic potential for heart failure. The effects of exercise on the cardiac and circulating lipidomes in comparison to disease are unclear. Lipidomic profiling was performed on hearts and plasma of mice subjected to swim endurance training or a cardiac disease model (moderate or severe pressure overload). Several sphingolipid species and phospholipids containing omega-3/6 fatty acids were distinctly altered in heart and/or plasma with exercise versus pressure overload. A subset of lipids was validated in an independent mouse model with heart failure and atrial fibrillation. This study highlights the adaptations that occur to lipid profiles in response to endurance training versus pathology and provides a resource to investigate potential therapeutic targets and biomarkers. : Tham et al. utilized a HPLC-ESI/MS/MS targeted lipidomics approach to show distinct remodeling of the cardiac and plasma lipidomes in response to exercise in comparison to heart disease stimuli. Differentially altered lipids were validated in a model with heart failure and atrial fibrillation and represent potential biomarkers and drug targets. Keywords: lipids, heart, exercise, physiological hypertrophy, pathological hypertrophy, atrial fibrillation, phospholipids, sphingolipids, biomarkers, treatment