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bioRxiv · 10.1101/2025.01.22.634271

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.
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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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Moon, R., Vogel, N., Mendelson, J. B., Hartweck, L., Carney, J., Kim, M., Gardner, M. K., Prisco, S., Prins, K.. 2025-01-24. 17β-Estradiol Counteracts Pathological Microtubule Remodeling To Enhance Cardiac Function. https://doi.org/10.1101/2025.01.22.634271

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