Project Summary:
Heart disease is the leading cause of death in both men and women in Wisconsin with huge emotional and economic impacts on families. Over 16,000 deaths were attributed to cardiovascular disease in our state, at an estimated annual cost of over $7.5 billion (Wisconsin Department of Health Services, 2017 statistics).
Myocardial infarction, also known as a “heart attack,” is the most common form of fatal heart disease in Wisconsin. Although most patients survive a heart attack the adult human heart fails to appropriately heal after the event, and many individuals who have experienced a heart attack will develop progressive heart failure. Patients who progress to end stage heart failure are limited to costly and sometimes problematic treatments such as heart transplant or implantation of left ventricular assist device, which is a device that partially or completely replaces the function of the failing heart. Importantly, age-adjusted mortality rates (AAMR, represented per 100,000 individuals) specifically related to heart failure are very high in the state of Wisconsin.
Wisconsin has among the highest AAMR for heart failure in Black and white men, and in Black women. Thus, there is great interest in identifying alternative therapies for treating heart failure with the goal of improving heart failure related mortality rates in Wisconsin.
The immune system plays an instrumental role in wound healing in many tissues and organs including the heart. One type of immune cell, the macrophage (Mɸ), has become a cell type of great interest in the healing process following a heart attack. While Mɸs are sometimes thought of as a single cell type, these cells can have very different characteristics and functions depending on their origin and environment.
This study focuses on investigating a gene that the research team hypothesizes influences the number and composition of Mɸ an individual has in their heart under normal conditions. Mechanisms identified in the study will be instrumental for understanding how Mɸ characteristics can be manipulated to promote a pro-reparative cellular state. Findings from this study will have the potential to improve morbidity and mortality outcomes in heart failure patient cohorts in Wisconsin and provide a reparative alternative to current therapies such as heart transplant and left ventricular assist device. Data generated from this pilot grant will be instrumental for applying for major grant funding aiming to understand the genetic underpinnings of cardiac resident Mɸ function.