KDM4D Overexpression Enhances Cardiac Regeneration and Mitigates Myocardial Damage in Response to Ischemic Injury

Thesis (Ph.D.)--University of Washington, 2020Protection of myocardium as a means to retain cardiac muscle after injury and prevent the development of heart failure has eluded the field for decades. We recently reported that lysine demethylase KDM4D could partially prevent and reverse cell cycle gene silencing, resulting in modest adult cardiac myocyte proliferation. In this study, we examined the role of KDM4D in response to myocardial infarction in the clinically relevant setting of adult mice by inducing overexpression of KDM4D coincident with MI. KDM4D improved cardiac function after MI, however not through proliferation. The primary benefit of KDM4D was the preservation of myocardium through reduced apoptosis. Gene expression and western blot analysis demonstrated an increase in several anti-apoptotic factors. Our findings suggest that KDM4D may potentiate a survival response and mitigate myocardial damage in response to ischemic injury, making it an attractive candidate for future therapeutic development