Gestational arsenite exposure alters maternal postpartum heart size and induces Ca2+ handling dysregulation in cardiomyocytes

Taube, N.; Steiner, M.; Ebenebe-Kasonde, O. V.; Kabir, R.; Garbus-Grant, H.; Alam El Din, S.-M.; Illingworth, E.; Wang, N.; Lin, B. L.; Kohr, M. J.

doi:10.1101/2024.09.25.615085

bioRxiv · 10.1101/2024.09.25.615085

Gestational arsenite exposure alters maternal postpartum heart size and induces Ca2+ handling dysregulation in cardiomyocytes

Taube, N.·Steiner, M.·Ebenebe-Kasonde, O. V.·Kabir, R.·Garbus-Grant, H.·Alam El Din, S.-M.·Illingworth, E.·Wang, N.·Lin, B. L.·Kohr, M. J.

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Abstract

Cardiovascular disease is the leading cause of mortality in the US. Studies suggest a role for environmental exposures in the etiology of cardiovascular disease, including exposure to arsenic through drinking water. Arsenic exposure during pregnancy has been shown to have effects on offspring, but few studies have examined impacts on maternal cardiovascular health. While our prior work documented the detrimental effect of arsenic on the maternal heart during pregnancy, our current study examines the effect of gestational arsenic exposure on the maternal heart postpartum. Timed-pregnant wild-type (C57BL/6J) mice were exposed to 0, 100 or 1000 {micro}g/L sodium arsenite (NaAsO2) via drinking water from embryonic day 2.5 (E2.5) until parturition. Postpartum heart structure and function was assessed via transthoracic echocardiography and gravimetric measurement. Hypertrophic markers were probed via qRT-PCR and western blot. Isolated cardiomyocyte Ca2+-handling and contraction were also assessed, and expression of proteins associated with Ca2+ handling and contraction. Interestingly, we found that exposure to either 100 or 1000 {micro}g/L sodium arsenite increased postpartum heart size at P12 vs. non-exposed postpartum controls. At the cellular level, we found altered cardiomyocyte Ca2+-handling and contraction. We also found altered expression of key contractile proteins, including -Actin and cardiac myosin binding protein C (cMyBP-c). Together, these findings suggest that gestational arsenic exposure impacts the postpartum maternal heart, possibly inducing long-term cardiovascular changes. Furthermore, these findings highlight the importance of reducing arsenic exposure during pregnancy, and the need for more research on the impact of arsenic and other environmental exposures on maternal heart health and adverse pregnancy events. New & NoteworthyGestational exposure to sodium arsenite at environmentally relevant doses (100 and 1000 {micro}g/L) increases postpartum heart size, and induces dysregulated Ca2+ homeostasis and impaired shortening in isolated cardiomyocytes. This is the first study to demonstrate that gestational arsenic exposure impacts postpartum heart structure and function beyond the exposure period.

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Taube, N., Steiner, M., Ebenebe-Kasonde, O. V., Kabir, R., Garbus-Grant, H., Alam El Din, S.-M., Illingworth, E., Wang, N., Lin, B. L., Kohr, M. J.. 2024-09-27. Gestational arsenite exposure alters maternal postpartum heart size and induces Ca2+ handling dysregulation in cardiomyocytes. https://doi.org/10.1101/2024.09.25.615085

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