Cardiovascular diseases are known to manifest different clinical symptoms in men and women. Basically this is due to gender-specific genotypes and sexual hormones. We studied gender specificity on the protein expression level in the mouse and human heart, with particular emphasis on the age-dependency of sex-specific protein expression. We first studied the heart proteome in female and male mice at 14 and 100 weeks of age using two-dimensional electrophoresis and mass spectrometry. Protein

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... rn comparison in young and old mice revealed 7 and 22 protein spots with sex-related expression profiles, respectively. Four proteins co-changed in both age groups. The variant protein spots were identified and revealed 10 distinct proteins and several isoforms thereof: α1-antitrypsin (3 isoforms), apolipoprotein A2 (2 isoforms), apolipoprotein A4 (3 isoforms), apolipoprotein E, apolipoprotein J (3 isoforms), carbonic anhydrase 2 (6 isoforms), desmin, nitrilase 1, peroxiredoxin 2 and Rho GDP dissociation inhibitor α (2 isoforms). More sex-related proteins were detected in old than in young mice. Through 2DE protein pattern and immunoblot comparisons, six of the variant proteins detected in mice were also observed to change in an age-and sex-dependent manner in the human heart. The age and/or gender-related proteins and species differences in this regard are discussed in terms of cardiovascular disease. Abbrevations: 2DE, two-dimensional gel electrophoresis; ApoJ, apolipoprotein J; ApoA4, apolipoprotein A4; ApoE, apolipoprotein E; ApoA2, apolipoprotein A2; ROS, reactive oxygen species; CA2, carbonic anhydrase 2; P-RhoGDI 1, Rho GDP dissociation inhibitor α; Prdx2, peroxiredoxin 2; AAT, α1-antitrypsin