The Impact of The Caveolin Scaffolding Domain Peptide on Cardiac Hypertrophy in Aged Ovariectomized Female Mice

Authors' Affiliations

Pearl McQuisstion,Department of Biological Sciences,East Tennessee State University Pamela Avendano-Rubi,Department of Biological Sciences,East Tennessee State University Kalynn Dalton,Department of Biological Sciences, East Tennessee State University Danisha Davis, Department of Biological Sciences, East Tennessee State University Krishna Singh, Department of Biomedical Sciences, 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

144

Name of Project's Faculty Sponsor

Cerrone Foster

Faculty Sponsor's Department

Biological Sciences

Classification of First Author

Undergraduate Student

Competition Type

Competitive

Type

Poster Presentation

Presentation Category

Science, Technology and Engineering

Abstract or Artist's Statement

Cardiovascular disease (CVD) has been one of the leading causes of death in the United States for over 100 years. When combined with stroke, they account for approximately 40% of all deaths. In addition, women have a poor prognosis and higher mortality rate from CVD injuries, which resulted in 1 out of every 5 female deaths in 2020. Additionally, it is known that CVD affects men and women differently and that most CVD research includes males as subjects. This leads to a gap in how CVD affects women with factors like pregnancy and menopause. This introduces the need for therapies that can restore cardiac function after injury in aging menopausal women. One such potential therapy is the caveolin-1 scaffolding domain peptide (CSD) which was previously shown to be cardioprotective but only studied in male models. This leads to a gap in knowledge on the effects of caveolin on female animal models. Previous work from the lab noted that CSD treatment in ovariectomized female mice with CVD resulted in a higher mortality rate compared to female mice with intact ovaries and male mice. The increased mortality was directly from the duration of estrogen loss post-ovariectomy, with five months acting as the critical point. Therefore, we examined the impact of the CSD peptide on cardiac hypertrophy in ovariectomized female mice 5 and 12 months post-ovariectomy. To examine this, female mice were ovariectomized (OVX) at 2.5 months of age. They were treated with isoproterenol (ISO; 400µg/kg/hr) 5 and 12 months post-ovariectomy for 3 days to simulate chronic heart failure and CSD (CSD at 50 mM). In addition, the SHAM group was infused with saline. Mice were euthanized and hearts were paraffin embedded for histological analysis. To examine cardiac hypertrophy, hearts were sectioned at 4µm and stained with Wheat Germ Agglutin to examine myocyte cross sectional area. Following staining, images of the heart were captured at 20X magnification, and the amount of hypertrophy was quantified by measuring the cross-sectional area using the NIS elements software program. Results are forthcoming; however, we expect increased myocyte cross sectional area in hearts treated with ISO and further increase in the OVX+ISO and OVX+ISO+CSD treated groups compared to SHAM animals in all groups. These data will highlight the need for consideration of sex differences in treatments and the role of the menopausal transition plays in heightened cardiovascular damage.

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

The Impact of The Caveolin Scaffolding Domain Peptide on Cardiac Hypertrophy in Aged Ovariectomized Female Mice

D.P. Culp Center Ballroom

Cardiovascular disease (CVD) has been one of the leading causes of death in the United States for over 100 years. When combined with stroke, they account for approximately 40% of all deaths. In addition, women have a poor prognosis and higher mortality rate from CVD injuries, which resulted in 1 out of every 5 female deaths in 2020. Additionally, it is known that CVD affects men and women differently and that most CVD research includes males as subjects. This leads to a gap in how CVD affects women with factors like pregnancy and menopause. This introduces the need for therapies that can restore cardiac function after injury in aging menopausal women. One such potential therapy is the caveolin-1 scaffolding domain peptide (CSD) which was previously shown to be cardioprotective but only studied in male models. This leads to a gap in knowledge on the effects of caveolin on female animal models. Previous work from the lab noted that CSD treatment in ovariectomized female mice with CVD resulted in a higher mortality rate compared to female mice with intact ovaries and male mice. The increased mortality was directly from the duration of estrogen loss post-ovariectomy, with five months acting as the critical point. Therefore, we examined the impact of the CSD peptide on cardiac hypertrophy in ovariectomized female mice 5 and 12 months post-ovariectomy. To examine this, female mice were ovariectomized (OVX) at 2.5 months of age. They were treated with isoproterenol (ISO; 400µg/kg/hr) 5 and 12 months post-ovariectomy for 3 days to simulate chronic heart failure and CSD (CSD at 50 mM). In addition, the SHAM group was infused with saline. Mice were euthanized and hearts were paraffin embedded for histological analysis. To examine cardiac hypertrophy, hearts were sectioned at 4µm and stained with Wheat Germ Agglutin to examine myocyte cross sectional area. Following staining, images of the heart were captured at 20X magnification, and the amount of hypertrophy was quantified by measuring the cross-sectional area using the NIS elements software program. Results are forthcoming; however, we expect increased myocyte cross sectional area in hearts treated with ISO and further increase in the OVX+ISO and OVX+ISO+CSD treated groups compared to SHAM animals in all groups. These data will highlight the need for consideration of sex differences in treatments and the role of the menopausal transition plays in heightened cardiovascular damage.