Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Effects of Sex and 17β-Estradiol on Cardiac Fibroblast Morphology and Signaling Activities in vitro

Version 1 : Received: 2 September 2021 / Approved: 6 September 2021 / Online: 6 September 2021 (17:24:51 CEST)

A peer-reviewed article of this Preprint also exists.

Watts, K.; Richardson, W.J. Effects of Sex and 17 β-Estradiol on Cardiac Fibroblast Morphology and Signaling Activities In Vitro. Cells 2021, 10, 2564. Watts, K.; Richardson, W.J. Effects of Sex and 17 β-Estradiol on Cardiac Fibroblast Morphology and Signaling Activities In Vitro. Cells 2021, 10, 2564.

Journal reference: Cells 2021, 10, 2564
DOI: 10.3390/cells10102564

Abstract

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 that has a stiffness much higher 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 sex-disaggregated analysis of changes in cellular morphology and relative concentrations of profibrotic signaling proteins in CFs cultured on 8kPa stiffness plates with and without 17-β estradiol (E2). Cyclic immunofluorescent analysis indicated that there is a negligible change in cellular morphology due to sex and E2 treatment and that the differences between male and female CFs are occurring 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.

Keywords

cardiac fibroblasts; sex-specific; estrogen; fibrosis; heart failure

Subject

ENGINEERING, Biomedical & Chemical Engineering

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