The Effects of Prolonged Sympathetic Stimulation on Cardiac Fibrosis in Estrogen Deficient Mice
Faculty Mentor
Cerrone Foster
Mentor Home Department
Biological Sciences
Short Abstract
The goal of this research is to evaluate the effects of estrogen loss on the development of fibrosis within the cardiac tissue and the exacerbation of the fibrosis due to chronic sympathetic stimulation. Cardiac fibrosis develops in the heart due to cardiac injury. Without the development of fibrosis, the integrity of the heart’s muscular wall would deteriorate. However, abnormal amounts of fibrosis can lead to decreased ejection fraction, arrythmias, and heart failure. Several studies show sex differences as well as changes across the menopause transition in women impact cardiovascular structure and function. Studies show that estrogen has cardioprotective effects but how this loss negatively impacts the heart following injury is still not clearly understood. Therefore, understanding the risk factors and disease development process is imperative for proper cardiac treatment, especially of women who experience loss of estrogen due to menopause and ovariectomy. Previous work in our lab examined the impact of estrogen loss on cardiac fibrosis with acute sympathetic stimulation after 7 days. We are extending those studies to examine chronic stimulation over a longer time of 28 days. Our hypothesis is that loss of estrogen exacerbates cardiac fibrosis and is further compounded by increased chronic sympathetic stimulation. An ovariectomized (OVX) mouse model was used in this research to simulate menopause and heart failure was simulated through chronic sympathetic stimulation by isoproterenol (ISO; 400µg/kg/hr), a β-adrenergic agonist. Mice were randomly selected into four treatment groups. At 2.5 months mice were ovariectomized (OVX) and received SHAM (mock) surgery. After 5 months mice were infused with ISO via a mini osmotic pump for 28 days (ISO, ISO+OVX) or saline (SHAM, OVX). Hearts were removed and embedded in paraffin for histological analysis. The hearts were sectioned at 4µm and stained for fibrosis using Masson’s Trichrome technique. A student’s t test will be used to demonstrate significance between comparable groups. Data is forthcoming. However, we expect increased fibrosis in the ISO and OVX+ISO groups at 28 days. Additional research is needed to elucidate the molecular pathways involved in the development of cardiac fibrosis with examination of matrix metalloproteinases at varying time points to better understand the development of cardiac pathophysiology in estrogen deficient models.
Category
Science, Technology and Engineering
Start Date
5-4-2024 3:30 PM
End Date
5-4-2024 4:30 PM
Location
D.P. Culp Center Room 219
The Effects of Prolonged Sympathetic Stimulation on Cardiac Fibrosis in Estrogen Deficient Mice
D.P. Culp Center Room 219
The goal of this research is to evaluate the effects of estrogen loss on the development of fibrosis within the cardiac tissue and the exacerbation of the fibrosis due to chronic sympathetic stimulation. Cardiac fibrosis develops in the heart due to cardiac injury. Without the development of fibrosis, the integrity of the heart’s muscular wall would deteriorate. However, abnormal amounts of fibrosis can lead to decreased ejection fraction, arrythmias, and heart failure. Several studies show sex differences as well as changes across the menopause transition in women impact cardiovascular structure and function. Studies show that estrogen has cardioprotective effects but how this loss negatively impacts the heart following injury is still not clearly understood. Therefore, understanding the risk factors and disease development process is imperative for proper cardiac treatment, especially of women who experience loss of estrogen due to menopause and ovariectomy. Previous work in our lab examined the impact of estrogen loss on cardiac fibrosis with acute sympathetic stimulation after 7 days. We are extending those studies to examine chronic stimulation over a longer time of 28 days. Our hypothesis is that loss of estrogen exacerbates cardiac fibrosis and is further compounded by increased chronic sympathetic stimulation. An ovariectomized (OVX) mouse model was used in this research to simulate menopause and heart failure was simulated through chronic sympathetic stimulation by isoproterenol (ISO; 400µg/kg/hr), a β-adrenergic agonist. Mice were randomly selected into four treatment groups. At 2.5 months mice were ovariectomized (OVX) and received SHAM (mock) surgery. After 5 months mice were infused with ISO via a mini osmotic pump for 28 days (ISO, ISO+OVX) or saline (SHAM, OVX). Hearts were removed and embedded in paraffin for histological analysis. The hearts were sectioned at 4µm and stained for fibrosis using Masson’s Trichrome technique. A student’s t test will be used to demonstrate significance between comparable groups. Data is forthcoming. However, we expect increased fibrosis in the ISO and OVX+ISO groups at 28 days. Additional research is needed to elucidate the molecular pathways involved in the development of cardiac fibrosis with examination of matrix metalloproteinases at varying time points to better understand the development of cardiac pathophysiology in estrogen deficient models.