Project Title

The Role of Estrogen Deficiency on Cardiovascular Disease following Chronic Sympathetic Stimulation

Authors' Affiliations

Hayley Seaton, Department of Biological Sciences, College of Arts and Sciences, East Tennessee State University, Johnson City, TN Krishna Singh, Department of Biomedical Sciences, College of Medicine, East Tennessee State University, Johnson City, TN Cerrone R. Foster, Department of Biological Sciences, College of Arts and Sciences, East Tennessee State University, Johnson City, TN

Location

White Top Mtn

Start Date

4-12-2019 9:00 AM

End Date

4-12-2019 2:30 PM

Poster Number

113

Faculty Sponsor’s Department

Biological Sciences

Name of Project's Faculty Sponsor

Dr. Cerrone Foster

Type

Poster: Competitive

Classification of First Author

Undergraduate Student

Project's Category

Biological Sciences, Cardiovascular System, Circulatory System, Cardiovascular Disease, Histology

Abstract Text

Cardiovascular disease is the leading cause of death with over 600,000 deaths per year. A key feature of heart failure is over stimulation of the beta-adrenergic receptors. Over stimulation of these receptors leads to changes in contractility of the heart, which can eventually lead to myocardial remodeling such as cardiomyocyte cell death (apoptosis). Prolonged activation and injury of the heart stimulates fibroblasts to repair the injured site and can lead to stiffening and scar formation. These changes in the heart are heightened in post-menopausal women as estrogen is depleted. Clinical trials have shown that estrogen has cardioprotective effects through its receptors: estrogen receptor alpha (ER-α) and estrogen receptor beta (ER-β). Though estrogen has been shown to be cardioprotective, studies have shown that hormone replacement therapy had little to no benefit to postmenopausal women with heart disease. These discrepancies lead to the need for more studies on how estrogen can protect the heart against failure. We therefore, examined the effects of estrogen deficiency and its role on cardiac structure and function following chronic β-adrenergic stimulation. Female mice (4 months of age) were treated with isoproterenol (ISO) (400μg/kg/h, subcutaneously) for 7 days one month after bilateral ovariectomy (OVX) at 3 months of age. Echocardiography and pulse wave doppler analysis was performed to examine cardiac function. Animals were then euthanized and hearts were isolated and paraffin embedded for histology analysis. Fibrosis was analyzed using Masson’s trichrome staining and apoptosis was analyzed with TUNEL assay. Ovariectomy did result in significant compromised cardiac function and ISO treatment exacerbated these results. Results from the echocardiography exam showed that ISO increased left ventricular diameter and that ovariectomy increased the diameter in a similar manner. Ovariectomized mice treated with ISO showed even greater increases in left ventricular diameter. The Doppler pattern results also showed a significant decrease in contraction time in the ISO and OVX+ISO groups compared to the OVX group alone. Surprisingly, Masson’s trichrome staining showed no significant change between the SHAM and ISO treated groups. The low amount of fibrosis could be attributed to the length of the ISO treatment. One-month post-ovariectomy may not be long enough to cause significant estrogen loss for the heart with effects on fibrosis. Extending the length of time post-ovariectomy before beginning isoproterenol treatment will be important to study the effects of estrogen loss on heart failure over time. We will analyze cardiac apoptosis and hypertrophy as further indicators of cardiac remodeling following ovariectomy and chronic beta-adrenergic stimulation. The results of this work can provide new information on heart disease in post menopausal women and alternative drug targets.

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Apr 12th, 9:00 AM Apr 12th, 2:30 PM

The Role of Estrogen Deficiency on Cardiovascular Disease following Chronic Sympathetic Stimulation

White Top Mtn

Cardiovascular disease is the leading cause of death with over 600,000 deaths per year. A key feature of heart failure is over stimulation of the beta-adrenergic receptors. Over stimulation of these receptors leads to changes in contractility of the heart, which can eventually lead to myocardial remodeling such as cardiomyocyte cell death (apoptosis). Prolonged activation and injury of the heart stimulates fibroblasts to repair the injured site and can lead to stiffening and scar formation. These changes in the heart are heightened in post-menopausal women as estrogen is depleted. Clinical trials have shown that estrogen has cardioprotective effects through its receptors: estrogen receptor alpha (ER-α) and estrogen receptor beta (ER-β). Though estrogen has been shown to be cardioprotective, studies have shown that hormone replacement therapy had little to no benefit to postmenopausal women with heart disease. These discrepancies lead to the need for more studies on how estrogen can protect the heart against failure. We therefore, examined the effects of estrogen deficiency and its role on cardiac structure and function following chronic β-adrenergic stimulation. Female mice (4 months of age) were treated with isoproterenol (ISO) (400μg/kg/h, subcutaneously) for 7 days one month after bilateral ovariectomy (OVX) at 3 months of age. Echocardiography and pulse wave doppler analysis was performed to examine cardiac function. Animals were then euthanized and hearts were isolated and paraffin embedded for histology analysis. Fibrosis was analyzed using Masson’s trichrome staining and apoptosis was analyzed with TUNEL assay. Ovariectomy did result in significant compromised cardiac function and ISO treatment exacerbated these results. Results from the echocardiography exam showed that ISO increased left ventricular diameter and that ovariectomy increased the diameter in a similar manner. Ovariectomized mice treated with ISO showed even greater increases in left ventricular diameter. The Doppler pattern results also showed a significant decrease in contraction time in the ISO and OVX+ISO groups compared to the OVX group alone. Surprisingly, Masson’s trichrome staining showed no significant change between the SHAM and ISO treated groups. The low amount of fibrosis could be attributed to the length of the ISO treatment. One-month post-ovariectomy may not be long enough to cause significant estrogen loss for the heart with effects on fibrosis. Extending the length of time post-ovariectomy before beginning isoproterenol treatment will be important to study the effects of estrogen loss on heart failure over time. We will analyze cardiac apoptosis and hypertrophy as further indicators of cardiac remodeling following ovariectomy and chronic beta-adrenergic stimulation. The results of this work can provide new information on heart disease in post menopausal women and alternative drug targets.