title: Comparative proteomic analysis reveals sex and estrogen receptor β effects in the pressure overloaded heart.
abstract: 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 involved in structure and suggests a link between female sex and cytoskeletal integrity. In males, a set of proteins was identified that associate with mitochondrial bioenergetics and energy supply. We confirmed protein regulation by immunoblotting analysis. In conclusion, the proteomic response of the heart to PO is significantly modulated by ERβ and sex. We put forward that the observed differences may identify sex-specific targets for the treatment of heart failure, contributing toward more personalized medical care.
authors.affiliation: Institute of Gender in Medicine, Center for Cardiovascular Research, and DZHK (German Center for Cardiovascular Research) , Berlin partner site, Charite University Hospital, 10117 Berlin, Germany.
authors.forename: Georgios
authors.initials: G
authors.lastname: Kararigas
authors.forename: Daniela
authors.initials: D
authors.lastname: Fliegner
authors.forename: Stefanie
authors.initials: S
authors.lastname: Forler
authors.forename: Oliver
authors.initials: O
authors.lastname: Klein
authors.forename: Carola
authors.initials: C
authors.lastname: Schubert
authors.forename: Jan-Åke
authors.initials: JÅ
authors.lastname: Gustafsson
authors.forename: Joachim
authors.initials: J
authors.lastname: Klose
authors.forename: Vera
authors.initials: V
authors.lastname: Regitz-Zagrosek
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D003251:Constriction, Pathologic / Q000503:physiopathology; D015180:Electrophoresis, Gel, Two-Dimensional; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006321:Heart / Q000503:physiopathology*; D015151:Immunoblotting; D008297:Male; D013058:Mass Spectrometry; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism*; D011312:Pressure; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D012737:Sex Factors
chemical_list: D047629:Estrogen Receptor beta; D020543:Proteome
keywords: estrogen receptor; hypertrophy; pressure overload; proteomic; sex differences