The Effect of Overexpression of EP3 Receptors on Troponin Levels and Cardiac Dysfunction in Mice
Alternative Title
Abstract
Cardiovascular disease is one of the leading causes of mortality globally and the number of people affected is rising. Cardiovascular disease encompasses disorders that affect the heart and vascular system. In particular, heart failure is a devastating and costly condition. Heart failure occurs when the heart cannot adequately pump blood and is characterized by cardiac remodeling. There are two main types of heart failure: heart failure with reduced ejection fraction and heart failure with preserved ejection fraction. In heart failure prostaglandin E2 is a known mediator of inflammation; however, it has been shown to have anti-inflammatory roles as well. Although other prostaglandin E2 receptor subtypes such as EP1, EP2, and EP4 are prevalent, only EP4 and EP3 are abundant in the heart. EP4 has been found to be protective and improve cardiac function after a myocardial infarction. In contrast, EP3 has been shown to be deleterious with data showing a decrease in myocardial calcium sensitivity, suggesting alterations in calcium handling proteins. This study will therefore examine if overexpression of EP3 receptors alters troponin expression and/or posttranslational modification leading to observed cardiac dysfunction. Left ventricular tissue from five five-week old transgenic mice and wildtype littermates, along with 15-week old transgenic mice and wildtype littermates will be harvested. Tissue samples will be homogenized and used for western blotting
using 12% PAGE. Phospho-Troponin I (cardiac) and total Troponin I primary antibodies will be used to assess phosphorylation. Densitometric analysis will be completed and data analyzed via T-tests with a P value<0.05 for significance. We hypothesize that troponin phosphorylation will be higher in the 15-week-old transgenic mice, associated with the overall decreased cardiac function.