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17β-Estradiol Counteracts Pathological Microtubule Remodeling To Enhance Cardiac Function

Moon, R.; Vogel, N.; Mendelson, J. B.; Hartweck, L.; Carney, J.; Kim, M.; Gardner, M. K.; Prisco, S.; Prins, K.

2025-01-24 physiology
10.1101/2025.01.22.634271 bioRxiv
Show abstract

The female-predominate sex hormone 17{beta}-estradiol exerts cardioprotective effects via multiple mechanisms. Available data demonstrate 17{beta}-estradiol modulates microtubule dynamics in vitro, but its effects on pathogenic microtubule remodeling in pressure-overloaded cardiomyocytes are unexplored. Here, we show 17{beta}-estradiol directly blunts microtubule polymerization in vitro, counteracts endothelin-mediated microtubule remodeling in iPSC-cardiomyocytes, and mitigates microtubule stabilization in pulmonary artery banded right ventricular cardiomyocytes. 17{beta}-estradiol treatment blunts cardiomyocyte and nuclear hypertrophy, restores t-tubule architecture, and prevents mislocalization of connexin-43 in RV cardiomyocytes of pulmonary artery banded rats. These cellular phenotypes are paired with significant improvements in RV function. Thus, we propose 17{beta}-estradiol exerts cardioprotective effects via direct modulation of microtubules in addition to its well ascribed signaling functions.

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