The Impact of the Timing and Estrogen Loss on Cardiac Myocyte Apoptosis in Cardiovascular Disease
Faculty Mentor
Cerrone Foster
Mentor Home Department
Biological Sciences
Short Abstract
Cardiovascular disease is the leading cause of death in both men and women worldwide. Studies have shown that ~18 million people have died in 2019, and 8.9 million of them are women. Despite these high numbers, CVD remains understudied in women compared to men. One characteristic of CVD is increased sympathetic activity resulting in increased cardiac contraction leading to an overworked heart. Apoptosis, known as programmed cell death, aids the body in removing damaged cells that are beyond repair. In the heart, apoptosis is usually present near regions of injury and because heart tissue does not regenerate, loss of these cells is detrimental to proper function. Estrogen has been observed to protect the heart from various forms of stress, including apoptosis. Furthermore, studies have shown increased apoptosis with aging and menopause. In this study we examined the impact of the duration of menopause on cardiac myocyte apoptosis. Our hypothesis is that prolonged timing and estrogen loss will increase cardiac myocyte apoptosis following acute sympathetic stimulation. Female mice underwent ovariectomy at 2.5 months or SHAM surgery. Either 1-month or 5-month post OVX mice were treated with isoproterenol (ISO; 400µg/kg/hr) for chronic sympathetic stimulation using mini osmotic pumps 1- and 5-months post ovariectomy for 7 days. Animals were euthanized, hearts removed, and embedded in paraffin for histological analysis. Heart sections (4um thick) were then stained using the TUNEL assay kit to determine the number of apoptotic positive cells. Nuclei were determined via Hoechst staining. Percent apoptosis was determined by the number of TUNEL positive cells per total nuclei using NIS elements software. Results from this work are still in progress. However, we expect the OVX and ISO groups to show significantly higher amounts of apoptosis compared to the SHAM group at 7 days and a greater increase in the OVX+ISO group at 5 months OVX. These results would demonstrate the strong impact of estrogen loss has on the structural integrity of the heart and how cell death is exacerbated by estrogen loss and injury. These data may also point to the possibility of increased consequence of heart failure in women at a later stage in menopause.
Category
Science, Technology and Engineering
Start Date
5-4-2024 2:30 PM
End Date
5-4-2024 3:30 PM
Location
D.P. Culp Center Room 219
The Impact of the Timing and Estrogen Loss on Cardiac Myocyte Apoptosis in Cardiovascular Disease
D.P. Culp Center Room 219
Cardiovascular disease is the leading cause of death in both men and women worldwide. Studies have shown that ~18 million people have died in 2019, and 8.9 million of them are women. Despite these high numbers, CVD remains understudied in women compared to men. One characteristic of CVD is increased sympathetic activity resulting in increased cardiac contraction leading to an overworked heart. Apoptosis, known as programmed cell death, aids the body in removing damaged cells that are beyond repair. In the heart, apoptosis is usually present near regions of injury and because heart tissue does not regenerate, loss of these cells is detrimental to proper function. Estrogen has been observed to protect the heart from various forms of stress, including apoptosis. Furthermore, studies have shown increased apoptosis with aging and menopause. In this study we examined the impact of the duration of menopause on cardiac myocyte apoptosis. Our hypothesis is that prolonged timing and estrogen loss will increase cardiac myocyte apoptosis following acute sympathetic stimulation. Female mice underwent ovariectomy at 2.5 months or SHAM surgery. Either 1-month or 5-month post OVX mice were treated with isoproterenol (ISO; 400µg/kg/hr) for chronic sympathetic stimulation using mini osmotic pumps 1- and 5-months post ovariectomy for 7 days. Animals were euthanized, hearts removed, and embedded in paraffin for histological analysis. Heart sections (4um thick) were then stained using the TUNEL assay kit to determine the number of apoptotic positive cells. Nuclei were determined via Hoechst staining. Percent apoptosis was determined by the number of TUNEL positive cells per total nuclei using NIS elements software. Results from this work are still in progress. However, we expect the OVX and ISO groups to show significantly higher amounts of apoptosis compared to the SHAM group at 7 days and a greater increase in the OVX+ISO group at 5 months OVX. These results would demonstrate the strong impact of estrogen loss has on the structural integrity of the heart and how cell death is exacerbated by estrogen loss and injury. These data may also point to the possibility of increased consequence of heart failure in women at a later stage in menopause.