Comparative proteomic analysis reveals sex and estrogen receptor β effects in the pressure overloaded heart.

In pressure overload (PO), sex differences in humans and rodents have been well documented and estrogen receptor (ER) β is considered cardioprotective. However, the underlying mechanisms are poorly understood. Our aim was to investigate sex- and ERβ-specific effects in protein abundance in PO employing a 2-dimensional gel electrophoresis/mass spectrometry-based proteomics approach. We hypothesized major sex differences and ERβ-specific alterations consistent with cardioprotection in females. Two-month old male and female wild-type (WT) and ERβ knockout (BERKO) mice were subjected to transverse aortic constriction (TAC) for 9 weeks (n = 4/group). In WT mice, hypertrophy was significantly more pronounced in males than females, while this sex difference was abolished in BERKO mice. We found 82 protein spots modulated between TAC and sham in WT males, 31 in WT females, 114 in BERKO males, and 87 in BERKO females (P ≤ 0.05). Our analysis revealed in WT and BERKO females an altered pattern of various proteins i...