APLN and pulmonary arterial hypertension: Its activation enhances the expression of BMPR2 and APLN, both of which are essential for vascular homeostasis and RV adaptation.314,315 Research in an MCT-PAH model demonstrates that estrogen replacement therapy in ovariectomized female rats significantly reduces RVH and PAP, while estrogen deficiency accelerates disease progression.313 These findings underscore the role of ERα in mitigating pulmonary vascular remodeling and preserving RV function.