17 β-estradiol treatment of male and female cardiac fibroblasts showed negligible changes in cellular morphology but produced varied sex-specific responses in profibrotic signaling proteins.
Does 17 β-estradiol alter cellular morphology and profibrotic signaling proteins in male and female cardiac fibroblasts?
Male and female cardiac fibroblasts exhibit intrinsic biochemical differences in profibrotic signaling responses to 17 β-estradiol, highlighting the need for sex-specific approaches in cardiac fibrosis research.
Several studies have demonstrated estrogen's cardioprotective abilities in decreasing the fibrotic response of cardiac fibroblasts (CFs). However, the majority of these studies are not sex-specific, and those at the cellular level utilize tissue culture plastic, a substrate with a much higher stiffness than physiological conditions. Understanding the intrinsic differences between male and female CFs under more physiologically "healthy" conditions will help to elucidate the divergences in their complex signaling networks. We aimed to do this by conducting a sex-disaggregated analysis of changes in cellular morphology and relative levels of profibrotic signaling proteins in CFs cultured on 8 kPa stiffness plates with and without 17 β-estradiol (E2). Cyclic immunofluorescent analysis indicated that there was a negligible change in cellular morphology due to sex and E2 treatment and that the differences between male and female CFs occur at a biochemical rather than structural level. Several proteins corresponding to profibrotic activity had various sex-specific responses with and without E2 treatment. Single-cell correlation analysis exhibited varied protein-protein interaction across experimental conditions. These findings demonstrate the need for further research into the dimorphisms of male and female CFs to develop better tailored sex-informed prevention and treatment interventions of cardiac fibrosis.
Watts et al. (Tue,) conducted a other in Cardiac fibrosis. 17 β-estradiol (E2) vs. Without 17 β-estradiol was evaluated on Changes in cellular morphology and relative levels of profibrotic signaling proteins. 17 β-estradiol treatment of male and female cardiac fibroblasts showed negligible changes in cellular morphology but produced varied sex-specific responses in profibrotic signaling proteins.
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