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The Role of Tip60 in Cardiac Calcium Signaling and Mitochondria Function

Exploring a new treatment for ischemic heart disease

Full Project Name:The Role of Tip60 in Cardiac Calcium Signaling and Mitochondria FunctionPrincipal Investigator:Xinrui Wang, PhD, Pharmacology and ToxicologyAward Amount:$49,757
Award Date
January2024
Project Duration:9 months

Project Summary:


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.

Outcomes & Lessons Learned:


  • Isolated heart cells from mice and found that inhibition of Tip60 improved cytosolic calcium homeostasis and diminished pathological changes in mitochondria
  • Improved understanding of how lysine acetyltransferase Tip60 functions in novel biological processes during myocardial infarction, highlighting the transition of the research focus of the project team from cardiac regeneration to calcium signaling and mitochondria function; the contributing goal of identifying Tip60 as a therapeutic target having the potential to treat ischemic heart disease, the leading cause of death in Wisconsin
  • Generated data showing the function of Tip60 in excitation-contraction-metabolism coupling, an important cardiac contractile mechanism, which will lead to an expanded research plan designed to reveal Tip60-dependent mechanistic pathways in cardiac pathophysiology and to assess further the translational potential of targeting Tip60 as a novel, multifactorial target for limiting the damaging effects of ischemic injury
  • Disseminated research findings regarding targeting Tip60 for heart repair through a presentation

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