Downstream of Egfr, we identified sex-dependent activation of PKC signaling in male and ERK/MAPK signaling in female as mediators of Ctgf expression.<h4>Conclusion</h4>Overall, the relevance of AngII-calcineurin signaling for pathophysiological effects in the vasculature differs between female and male mice, suggesting both sexes require customized prevention and treatment strategies for cardiovascular disorders. Here, CCN2 is linked to cardiovascular disorder.