Effect of estradiol on Ca2+ handling proteins in hypertrophied H9c2-derived myotubes

Abstract

Cardiac hypertrophy is characterized by abnormal growth of muscle mass, accompanied by dysregulations in cell structure and function, and can lead to heart failure. Some of the main changes that hypertrophic cells undergo are sarcomere disorganization, loss of T tubules, alterations in Ca2+ management, and cardiac contractility. There is a higher prevalence of cardiovascular diseases in young and middle-aged men compared to women, which is why female sex hormones (being 17β-Estradiol the main circulating female sex hormone) are considered to play a cardioprotective role. Cardiac hypertrophy, its molecular mechanisms and therapeutic strategies have traditionally been studied in different in vivo and in vitro models. Each model has advantages and disadvantages, such as challenging maintenance in primary cells or lack of complete cardiac phenotype in immortalized cell lines. The H9c2 cell line can be differentiated into myotubes, using retinoic acid as the inducing agent, to have a phenotype more cardiac-like. In this project it was standardized a model of hypertrophied H9c2-derived myotubes induced by angiotensin II, and the model was used to assess the cardioprotective role of pretreatment with 17β-Estradiol in terms of inflammation markers, gene expression of Ca2+ regulatory proteins, assessed by qPCR, and cell hypertrophy assessed by confocal microscopy. It was observed an attenuation of hypertrophic phenotype in differentiated myotubes with 17β-Estradiol pretreatment.