Hemanthakumar et al. show that risk factors for cardiovascular diseases (red) trigger molecular changes (red arrows) in cardiac endothelial cells (top cell in the central circle). This increases the expression levels of genes related to cellular aging (bottom right) and mesenchymal identity (bottom left). Exercise (blue) can protect against cardiovascular diseases by repressing these molecular changes (blue flat-ended arrow). Figure created using BioRender.com.