The Impact of Sex Differences, Estrogen loss, and Caveolin on Cardiac Myocyte Apoptosis Following Sympathetic Stimulation

Authors' Affiliations

Juliana Barnie, Department of Biological Sciences, Reagan Doner, Department of Biological Sciences, Cristiana Faith-Marie Martinez, Department of Biological Sciences, Kara Satterfield, Department of Biological Sciences, Department of Krishna Singh, Biomedical Sciences, East Tennessee State University, Johnson City, TN 37614.

Location

D.P. Culp Center Ballroom

Start Date

4-5-2024 9:00 AM

End Date

4-5-2024 11:30 AM

Poster Number

91

Name of Project's Faculty Sponsor

Cerrone Foster

Faculty Sponsor's Department

Biomedical Sciences

Classification of First Author

Undergraduate Student

Competition Type

Competitive

Type

Poster Presentation

Presentation Category

Health

Abstract or Artist's Statement

Cardiovascular disease (CVD) is the leading cause of death for both men and women globally, with 18 million lives lost annually. CVD is characterized by increased sympathetic stimulation via β-adrenergic receptor stimulation in the heart that contributes to increased contractility and heart failure. While this disease is detrimental for both sexes, menopausal women are at a greater risk for CVD than aged- matched males, suggesting there are other factors besides sex differences contributing to the disease. This decline in overall cardiac performance is in part due to cardiac remodeling through apoptotic mechanisms. Increased cardiac myocyte apoptosis, also known as programmed cell death, leads to loss of cells in the heart. The caveolin scaffolding domain peptide (CSD) has a positive effect on structural changes caused by sympathetic stimulation by regulating anti-apoptotic pathways in response to cardiac stress. CSD treatment has also been shown to be cardioprotective however studies were performed only in male mice. The purpose of this study is to determine differences in cardiac myocyte apoptosis in male and female mice following sympathetic stimulation and estrogen loss and the impact of CSD. For this study female mice were ovariectomized (OVX) 2.5-months and allowed estrogen depletion for 5 months. Animals were then treated with isoproterenol (ISO; 400µg/kg/day) continuously for 3 days using mini osmotic pumps in addition to the caveolin scaffolding protein (CSD at 50 mM) Mice were euthanized and hearts were excised for histological analysis. Heart sections (4µm thick) were then stained for apoptosis with the in-situ cell death detection kit. Data is still forthcoming, but preliminary results indicate that OVX+ISO and OVX+ISO + CSD group have a greater percentage of cardiomyocyte apoptosis. There was higher mortality in the OVX+ISO+CSD group suggesting that CSD offers minimal protection from cardiac damage in aged ovariectomized females. Male cardiomyocytes show lower cardiomyocyte apoptosis following ISO and CSD treatment than aged matched female mice. Initial results point to the sex specific nature of cardiovascular disease and the cardioprotective nature of estrogen in female mice. The expected outcomes highlight the need for further exploration into the influential role of estrogen and sex in cardiac remodeling.

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Apr 5th, 9:00 AM Apr 5th, 11:30 AM

The Impact of Sex Differences, Estrogen loss, and Caveolin on Cardiac Myocyte Apoptosis Following Sympathetic Stimulation

D.P. Culp Center Ballroom

Cardiovascular disease (CVD) is the leading cause of death for both men and women globally, with 18 million lives lost annually. CVD is characterized by increased sympathetic stimulation via β-adrenergic receptor stimulation in the heart that contributes to increased contractility and heart failure. While this disease is detrimental for both sexes, menopausal women are at a greater risk for CVD than aged- matched males, suggesting there are other factors besides sex differences contributing to the disease. This decline in overall cardiac performance is in part due to cardiac remodeling through apoptotic mechanisms. Increased cardiac myocyte apoptosis, also known as programmed cell death, leads to loss of cells in the heart. The caveolin scaffolding domain peptide (CSD) has a positive effect on structural changes caused by sympathetic stimulation by regulating anti-apoptotic pathways in response to cardiac stress. CSD treatment has also been shown to be cardioprotective however studies were performed only in male mice. The purpose of this study is to determine differences in cardiac myocyte apoptosis in male and female mice following sympathetic stimulation and estrogen loss and the impact of CSD. For this study female mice were ovariectomized (OVX) 2.5-months and allowed estrogen depletion for 5 months. Animals were then treated with isoproterenol (ISO; 400µg/kg/day) continuously for 3 days using mini osmotic pumps in addition to the caveolin scaffolding protein (CSD at 50 mM) Mice were euthanized and hearts were excised for histological analysis. Heart sections (4µm thick) were then stained for apoptosis with the in-situ cell death detection kit. Data is still forthcoming, but preliminary results indicate that OVX+ISO and OVX+ISO + CSD group have a greater percentage of cardiomyocyte apoptosis. There was higher mortality in the OVX+ISO+CSD group suggesting that CSD offers minimal protection from cardiac damage in aged ovariectomized females. Male cardiomyocytes show lower cardiomyocyte apoptosis following ISO and CSD treatment than aged matched female mice. Initial results point to the sex specific nature of cardiovascular disease and the cardioprotective nature of estrogen in female mice. The expected outcomes highlight the need for further exploration into the influential role of estrogen and sex in cardiac remodeling.