The Impact of Estrogen Loss on Caveolin Expression and Cardiac Myocyte Apoptosis in Ovariectomized Mice Following Chronic Sympathetic Stimulation.
Abstract
Cardiovascular diseases remain the top cause of death globally accounting for 19.91million global deaths in 2021. Compared to premenopausal women and age-matched males, post-menopausal women have the highest risk of CVD with poor prognosis due to estrogen deficiency. Beta-Adrenergic Receptor signaling is a major regulator of heart function and dysregulation of β -AR is a key feature in CVD patients. Caveolae and caveolins coordinate cell signaling activities in various cells, including cardiovascular system cells. Caveolins, by co-localizing with estrogen receptors and β-AR in the heart, contribute to maintaining healthy cardiac function. The caveolin binding component, Caveolin scaffolding domain (CSD), is used as treatment for heart disease and shown to be beneficial in animal models, but most studies focus on male mice, leaving a gap in post-menopausal females. Our lab previously showed CSD treatment increased mortality and heart dysfunction in ovariectomized mice with heart failure, contrasting the beneficial effects of CSD in male mice. The negative effect of CSD directly correlated to the duration of estrogen loss. Here, we investigate how the duration of estrogen loss impacts cardiac remodeling and caveolin expression in ovariectomized mice with heart failure. Female mice underwent ovariectomy (OVX) at age 2.5months with heart failure induced via isoproterenol(400µg/kg/hr.) for 3 days and CSD treatment 5 and 12months post OVX. After treatment, they were euthanized, and their heart was removed. Cardiomyocyte apoptosis and hypertrophy were assessed by TUNEL and WGA staining. Using NIS software, apoptosis and hypertrophy were quantified. Caveolin expressions were analyzed using Western blotting. We observed CSD treatment significantly increased hypertrophy and apoptosis in mice with prolonged estrogen loss. Protein analysis results are forthcoming, but caveolin levels are expected to be low in ovariectomized mice and further decreased in aged ovariectomized mice. This highlights the importance of timing estrogen loss in heart function and therapeutic interventions.
Start Time
16-4-2025 2:30 PM
End Time
16-4-2025 3:30 PM
Room Number
304
Presentation Type
Oral Presentation
Presentation Subtype
Grad/Comp Orals
Presentation Category
Health
Faculty Mentor
Cerrone Foster
The Impact of Estrogen Loss on Caveolin Expression and Cardiac Myocyte Apoptosis in Ovariectomized Mice Following Chronic Sympathetic Stimulation.
304
Cardiovascular diseases remain the top cause of death globally accounting for 19.91million global deaths in 2021. Compared to premenopausal women and age-matched males, post-menopausal women have the highest risk of CVD with poor prognosis due to estrogen deficiency. Beta-Adrenergic Receptor signaling is a major regulator of heart function and dysregulation of β -AR is a key feature in CVD patients. Caveolae and caveolins coordinate cell signaling activities in various cells, including cardiovascular system cells. Caveolins, by co-localizing with estrogen receptors and β-AR in the heart, contribute to maintaining healthy cardiac function. The caveolin binding component, Caveolin scaffolding domain (CSD), is used as treatment for heart disease and shown to be beneficial in animal models, but most studies focus on male mice, leaving a gap in post-menopausal females. Our lab previously showed CSD treatment increased mortality and heart dysfunction in ovariectomized mice with heart failure, contrasting the beneficial effects of CSD in male mice. The negative effect of CSD directly correlated to the duration of estrogen loss. Here, we investigate how the duration of estrogen loss impacts cardiac remodeling and caveolin expression in ovariectomized mice with heart failure. Female mice underwent ovariectomy (OVX) at age 2.5months with heart failure induced via isoproterenol(400µg/kg/hr.) for 3 days and CSD treatment 5 and 12months post OVX. After treatment, they were euthanized, and their heart was removed. Cardiomyocyte apoptosis and hypertrophy were assessed by TUNEL and WGA staining. Using NIS software, apoptosis and hypertrophy were quantified. Caveolin expressions were analyzed using Western blotting. We observed CSD treatment significantly increased hypertrophy and apoptosis in mice with prolonged estrogen loss. Protein analysis results are forthcoming, but caveolin levels are expected to be low in ovariectomized mice and further decreased in aged ovariectomized mice. This highlights the importance of timing estrogen loss in heart function and therapeutic interventions.