(A) Sex differences in cardiac cell type composition. The adult human heart is approximately 80% cardiomyocytes by mass, but also contains a plethora of other cell types, including fibroblasts, endothelial cells, and immune cells. Sex differences exist most notably in the relative proportion of cardiomyocytes, endothelial cells, and lymphoid cells. Proportions are based on data from single-cell RNA sequencing study performed by Litviňuková et al. (28). Cell types are ordered according to decreasing relative proportions in the female heart from left to right. Adapted with permission from Walker et al. (29). (B) Enriched cardiomyocyte signaling pathways in female hearts. PKA and Akt activity are enhanced in females at baseline. Proteins in pink have been directly shown to be enhanced in female hearts at baseline; proteins in gray are implicated based on the pathways activated. PKA phosphorylates proteins involved in contractility, while Akt regulates protein homeostasis. β1-AR, β₁-adrenergic receptor; Gαs, Gα stimulatory protein; LTCC, L-type calcium channel; RyR2, ryanodine receptor 2; TnI, troponin I; RTK, receptor tyrosine kinase; FoxO, forkhead box protein O.