Project Title

The Impact Of Long Term Ovariectomy On Diastolic Function And Fibrosis Following Chronic Sympathetic Stimulation In Mice

Authors' Affiliations

Erin Moore, Department of Biological Sciences, College of Arts and Sciences, East Tennessee State University, Johnson City, TN.

Location

Culp Room 210

Start Date

4-6-2022 10:00 AM

End Date

4-6-2022 10:15 AM

Faculty Sponsor’s Department

Biological Sciences

Name of Project's Faculty Sponsor

Cerrone Foster

Additional Sponsors

Krishna Singh, Gerardo Arceo Gomez

Classification of First Author

Undergraduate Student

Competition Type

Non-Competitive

Type

Boland Symposium

Project's Category

Cardiovascular Disease

Abstract or Artist's Statement

Cardiovascular Disease (CVD) accounts for the leading number of deaths worldwide. Prior to menopause, women exhibit lower rates of CVD compared to age-matched men, however, risks for women increase with menopause. Studies show that estrogen loss and age exacerbate cardiac Beta-adrenergic receptor (β-AR) signaling and contractile function. We, therefore, hypothesized that prolonged estrogen deficiency and chronic β-adrenergic stimulation cause a decrease in cardiac function and increases in fibrosis in aged female hearts. Female mice underwent ovariectomy (OVX) or SHAM surgery at 10 weeks old and after 12-months post-surgery, were infused with Isoproterenol (ISO; 400 μg/kg/hr) via mini osmotic pumps in order to induce chronic β-adrenergic stimulation. Transthoracic echocardiography was performed on the animals after 3 days of ISO treatment and pulse wave Doppler tracings of the mitral valve were used to measure heart rate (HR), isovolumic contraction time (IVCT), ejection time (ET), and isovolumic relaxation time (IVRT). Hearts were sectioned (4µm) and stained using Masson’s Trichrome procedure to observe the amount of fibrosis. Doppler analysis 12-month post-OVX revealed that OVX exacerbates contractile cardiac function. Results showed a significant increase in the ET for intact females treated with ISO (SHAM+ISO) compared with intact females (SHAM) as well as a significant decrease for ovariectomized females (OVX) compared to intact females (SHAM). The results also showed that the IVRT significantly decreased in OVX groups compared to intact females (SHAM). Similarly, intact mice (SHAM) treated with ISO (SHAM+ISO) showed a significant decrease in IVRT compared to the SHAM group. Comparing OVX and OVX+ISO we saw no significant change in the results for IVRT or ET. Results showed no significant difference in IVTC among any of the treatment groups. While we expected the percentage of fibrosis in the OVX and ISO treatments to experience increased fibrosis and while there was a trend toward decreased fibrosis in OVX and OVX+ISO groups, our results did not show a significant difference in the groups or significant differences in SHAM compared to SHAM+ISO. Our results highlight the impact depletion of estrogen levels and aging has on cardiac function. This work demonstrates the need for further research on cardiac estrogen deficiency mechanisms and the long-term effects during both CVD and menopause.

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Apr 6th, 10:00 AM Apr 6th, 10:15 AM

The Impact Of Long Term Ovariectomy On Diastolic Function And Fibrosis Following Chronic Sympathetic Stimulation In Mice

Culp Room 210

Cardiovascular Disease (CVD) accounts for the leading number of deaths worldwide. Prior to menopause, women exhibit lower rates of CVD compared to age-matched men, however, risks for women increase with menopause. Studies show that estrogen loss and age exacerbate cardiac Beta-adrenergic receptor (β-AR) signaling and contractile function. We, therefore, hypothesized that prolonged estrogen deficiency and chronic β-adrenergic stimulation cause a decrease in cardiac function and increases in fibrosis in aged female hearts. Female mice underwent ovariectomy (OVX) or SHAM surgery at 10 weeks old and after 12-months post-surgery, were infused with Isoproterenol (ISO; 400 μg/kg/hr) via mini osmotic pumps in order to induce chronic β-adrenergic stimulation. Transthoracic echocardiography was performed on the animals after 3 days of ISO treatment and pulse wave Doppler tracings of the mitral valve were used to measure heart rate (HR), isovolumic contraction time (IVCT), ejection time (ET), and isovolumic relaxation time (IVRT). Hearts were sectioned (4µm) and stained using Masson’s Trichrome procedure to observe the amount of fibrosis. Doppler analysis 12-month post-OVX revealed that OVX exacerbates contractile cardiac function. Results showed a significant increase in the ET for intact females treated with ISO (SHAM+ISO) compared with intact females (SHAM) as well as a significant decrease for ovariectomized females (OVX) compared to intact females (SHAM). The results also showed that the IVRT significantly decreased in OVX groups compared to intact females (SHAM). Similarly, intact mice (SHAM) treated with ISO (SHAM+ISO) showed a significant decrease in IVRT compared to the SHAM group. Comparing OVX and OVX+ISO we saw no significant change in the results for IVRT or ET. Results showed no significant difference in IVTC among any of the treatment groups. While we expected the percentage of fibrosis in the OVX and ISO treatments to experience increased fibrosis and while there was a trend toward decreased fibrosis in OVX and OVX+ISO groups, our results did not show a significant difference in the groups or significant differences in SHAM compared to SHAM+ISO. Our results highlight the impact depletion of estrogen levels and aging has on cardiac function. This work demonstrates the need for further research on cardiac estrogen deficiency mechanisms and the long-term effects during both CVD and menopause.