Project Description Narrative:
Ischemic heart disease is the leading cause of mortality in Wisconsin, accounting for 15% of all deaths in the state. 16% of all hospitalizations in Wisconsin were related to cardiac diagnoses, accounting for over $2.5 billion in associated charges. In addition, disparities in cardiac ischemia remain between racial and ethnic populations in Wisconsin; for instance, Native and African Americans have higher mortality rates than their White counterparts. A myocardial infarction (MI) happens when the coronary artery is blocked, preventing delivery of blood to the heart muscle; following an MI, adverse cardiac remodeling occurs, causing thinning of the left ventricular (LV) wall, LV dilation and impaired contractility, progression of which is linked to increased death or hospitalization due to heart failure.
This massive clinical problem would be significantly ameliorated by the development of strategies to protect, regenerate, and re-muscularize the diseased/injured myocardium. At the cellular and molecular levels, MI leads to adverse cardiac remodeling resultant from altered transcriptional, structural, and electrophysiological signaling pathways within heart muscle cells, i.e., cardiomyocytes (CMs). Although approaches are emerging to protect against the damaging effects of MI by modulating signaling pathways that regulate the cell-cycle, apoptosis, electrical excitation, Ca2+ handling, and cross-bridge cycling in CMs, few molecular factors are known to be involved in more than one of these mechanisms. The goal of this project is to identify a pleiotropic upstream factor that regulates multiple pathophysiological pathways, aiming to provide an optimally efficient approach for treating ischemic heart disease.