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

In pressure overload (PO), sex differences in humans and rodents have been well documented and estrogen receptor (ER) ß is considered cardioprotective. However, the underlying mechanisms are poorly understood. Our aim was to investigate sex- and ERß-specific effects in protein abundance in PO employing a 2-dimensional gel electrophoresis/mass spectrometry-based proteomics approach. We hypothesized major sex differences and ERß-specific alterations consistent with cardioprotection in females. Two-month old male and female wild-type (WT) and ERß 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 ERß 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.

Individualized proteomics.

Human individuals differ from one another in almost all of their genes due to single nucleotide polymorphisms (SNPs). When the maternal and the paternal genomes become combined in a F1 individual, the two alleles of each gene represent arbitrary combinations. In consequence, individuals show high variability in protein expression. Furthermore, within a proteome, the proteins form networks of protein-protein interactions. These networks differ between individuals in robustness against genetic or/and environmental perturbation due to polymorphisms, which differ in type and composition between individuals, and modify the arrangement of proteins in the proteomic network. As a general conclusion, the robustness of a human individual against diseases may depend on the structure and expression of the protein-protein interaction network that varies in its functional efficiency between individuals due to "network-polymorphisms". This article is part of a Special Issue entitled: 20years of Proteomics in memory of Viatliano Pallini. Guest Editors: Luca Bini, Juan J. Calvete, Natacha Turck, Denis Hochstrasser and Jean-Charles Sanchez.