Abstract 15411: Estrogen Receptor β Mediates Sex Differences in the Proteomic Response of the Heart to Pressure Overload
Sex differences in the response of the heart to pressure overload (PO) have pointed to estrogen receptor (ER) β, which may be cardioprotective. However, the underlying mechanisms are incompletely defined. In a proteomic analysis of PO-induced hypertrophy, we hypothesized significant sex differences mediated by ERβ. Two-month-old C57BL6 male (M) and female (F) wild-type (WT) and ERβ knockout (BERKO) mice were subjected to transverse aortic constriction (TAC) or sham surgery (n = 4/group). The proteome of left ventricular samples was separated by high-resolution 2-dimensional polyacrylamide gel electrophoresis followed by mass spectrometry. The proteomic data were analyzed with empirical Bayesian-based linear models using R/Bioconductor. Nine weeks after TAC, heart-weight-to-tibia-length ratio was significantly higher in WT M (TAC vs. sham 128%; P < 0.05) than in WT F (TAC vs. sham 54%; P < 0.05) mice (interaction P < 0.001), while this difference in BERKO mice between M (TAC vs. sham 53%; P < 0.05) and F (TAC vs. sham 55%; P < 0.05) was abolished (interaction P = 0.5). Following quality assessment, background correction and normalization of the proteomic data, 795 left ventricular protein spots were identified and analyzed. Our comparative proteomic analysis revealed that in WT M and F mice 82 and 31 protein spots, respectively, differed between sham and TAC (P ≤ 0.05). In BERKO M and F mice we found 114 and 87 altered protein spots, respectively (P ≤ 0.05). Mitochondrial bioenergetics-related proteins, such as trifunctional enzyme subunit family members, were repressed in M-WT-TAC mice, while cytoskeletal proteins were induced in F-WT-TAC mice. On the other hand, heat shock proteins were induced in both M and F-BERKO-TAC mice. Candidates in metabolic, mitochondrial and cytoskeletal pathways were selected for validation of the proteomic analysis by means of Western blotting. We conclude that ERβ mediates sex-specific remodeling playing a major role in the proteomic response of the heart to PO. In particular, metabolic and mitochondrial proteins are repressed in males but maintained in females. We expect that our study will be a useful resource for the unraveling of the effects of sex and ERβ in PO.
Author Disclosures: G. Kararigas: None. D. Fliegner: None. S. Forler: None. O. Klein: None. C. Schubert: None. J. Klose: None. V. Regitz-Zagrosek: None.
- © 2014 by American Heart Association, Inc.