Crossing a Fine Line: Disrupted Intracellular Calcium Handling in the Myocardium of a Mouse Model of Perimenopause

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University of Guelph


After menopause, acute myocardial infarction (AMI) outcomes are worse in women than age-matched men, a phenomenon attributed to the decline in ovarian estrogen production. Estrogens protect against cardiovascular disease (CVD) before menopause, but how the heart changes and the molecular basis for the elevated risk of poor AMI outcomes after menopause is unclear. Calcium (Ca2+) plays a key role in the stress response of the heart and dysregulation of Ca2+ handling can worsen injury associated with AMI. No studies have examined the changes in Ca2+ handling during the perimenopausal phase and no studies have used a postmenopausal model in which perimenopause was a component. Using a mouse model of menopause that includes a perimenopausal transition, we found that Ca2+ handling disruption occurs early in the perimenopausal transition, coinciding with the altered expression and post-translational modifications of key Ca2+ handling proteins. Comparing these findings to an ovariectomised mouse model of menopause we found postmenopausal remodelling of the heart is influenced by the path to menopause. These data provide a mechanistic basis for the increased risk of AMI adverse outcomes in postmenopausal women.



perimenopause, menopause, calcium, cardiac, VCD