Our finding that aging, obesity, and pressure overload induce mesenchymal gene programs in cardiac ECs adds to the increasing evidence that activated endothelial TGF-β signaling and acquisition of mesenchymal features play an important role in the development of EC dysfunction and cardiac diseases (Kovacic et al., 2019; Chen et al., 2015; Chen et al., 2019; Xiong et al., 2018). This evidence concerns the gene TGFB1 and obesity due to melanocortin 4 receptor deficiency.