Análise comparativa do proteoma do tecido cardíaco de camundongos fêmeas jovens, idosas e idosas tratadas com estradiol

Abstract

Introduction: Aging is a physiological and multifactorial process characterized by the progressive loss of anatomical and functional integrity, which leads to an increased risk of cardiovascular diseases (CVDs). It can be inferred that cardiac aging affects pathophysiological pathways of CVD development in both sexes due to structural and functional remodeling of the heart. In this sense, postmenopausal women stand out, who present a higher cardiac risk due to the reduction in the levels of estrogen hormones, which are associated with cardioprotection. The molecular mechanisms and proteins involved in the cardiac tissue during natural aging of females mice and the effects of estrogen (E2) are not yet well defined. Objective: To evaluate the proteomic changes in cardiac tissue in young, elderly and elderly female mice treated with E2. Methodology: Wild female C57BL / 6J mice aged 10 to 12 weeks were used for the young group, aged 22 to 24 months for the elderly and estradiol (E2)-treated elderly females (7 days of treatment with E2 subcutaneously). After treatment, the animals were euthanized and had the apex and base of the heart collected for further analysis. Results: In cardiac tissue of older females, there was an increase in cardiomyocyte diameter, extracellular space and AT1r protein expression when compared to young group. Proteomic analysis of senescence showed proteins positively related to muscle fiber contraction, such as Myh7 and Myl6, which suggest an increase in cardiac muscle contraction force in older females. Another point observed was the involvement of genes related to cellular homeostasis, which was impaired in aging. Analyzing the E2 treatment from the proteomic perspective, it was found 7 upregulated genes related to aerobic respiration functions, oxirreduction process and synthesis of mitochondrial ATP coupled with electron transport, suggesting a general improvement of cellular metabolism after treatment with E2. Interestingly, the protein S100a10 was present as the highest up-regulated by senescence when comparing young and old animals, and at the same time also had the highest down-regulation after E2 treatment when comparing elderly group to elderly treated with E2. Finally, Western blot analysis showed a reduction in the expression of pro-oxidant enzymes such as Gp91 and SOD2 in females treated with E2. Conclusions: Proteomics has been shown to be an efficient technique for linking protein and gene expression variations with CVDs. The results reinforced cellular imbalance in senescence, presenting a deregulation of cellular chemical homeostasis and a higher recruitment of proteins related to smooth muscle contraction. Acute treatment with E2 led to a reduction in mitochondrial ROS production and a relationship to improved overall cell metabolism, more abundant ATP production and more efficient cellular respiration. Additionally, treatment with E2 in senescence demonstrated antihypertrophic effects. Additional studies are needed to elucidate the role of S100a10 and other proteins identified in this study in natural aging and its modulation by E2. This paper provides a basis for the development of new studies on estrogen hormone treatment and its correlation with CVDs.