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1Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham, Birmingham, AL, United States 2Molecular and Cellular Pathology, Department of Pathology, The University of Alabama at Birmingham, Birmingham, AL, United States 3Department of Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, AL, United States 4Center for Translational Medicine, Temple University, Philadelphia, PA, United States Background: Endothelial cells (ECs) play a critical role in the maintenance of vascular homeostasis and in heart function. It was shown that activated fibroblast-derived exosomes impair cardiomyocyte function in hypertrophic heart, but their effect on ECs is not yet clear. Thus, we hypothesized that activated cardiac fibroblast-derived exosomes (FB-Exo) mediate EC dysfunction, and therefore modulation of FB-exosomal contents may improve endothelial function. ....