Extracellular vesicle proteome from cardiac muscle critical for protection against obesity in female mice

Dysregulation of ER has been linked with increased metabolic and cardiovascular disease risk. Uncovering the impact of ERα deficiency in specific tissues has implications for understanding the role ERα in normal physiology and disease, the increased disease risk in postmenopausal women, and the design of tissue-specific ERα-based therapies for a range of pathologies including cardiac disease and cancer. Cardiac myocyte-specific ER knockout mice (ERHKO) were generated to assess the role of ERα in the heart. Female ERHKO mice displayed a mild cardiac phenotype, but unexpectedly, the most striking phenotype was obesity in female ERHKO but not male ERHKO mice. We identified contractile dysfunction, metabolic and lipid dysregulation in hearts of female ERHKO mice. We also show that extracellular vesicles (EVs) collected from the perfusate from Langendorff-isolated hearts from female ERHKO mice contained distinct proteins with functions related to muscle, metabolic and fatty acid dysregulation.