Dual Filament Control of Myocardial Power and Hemodynamics

Cardiovascular disease accounts for 1 in 3 deaths in the United States and costs the country >$300 billion per year (2016 American Heart Association Statistical Update). Major disease subgroups include myocardial ischemia, vascular disease, and heart failure with many patients presenting with more than one condition. For example, myocardial ischemia often leads to heart failure which in turn can worsen vascular disease. Treatment options for the millions of Americans who have cardiovascular disease are currently limited by inadequate understanding of cardiovascular biology and pathophysiology. Animal models of cardiovascular disease can be used in many research projects but biospecimens from patients are required for translational studies. Blood samples can be obtained with minimal risk from most cardiovascular patients. Myocardial and vascular specimens are often removed as part of standard care during clinical procedures. This application focuses on the biophysical mechanisms that regulate myocardial power output. The experiments test how (1) modifications to regulatory proteins on the thin filament modulate cooperative activation, and (2) phosphorylation of myosin binding protein C regulates myofilament-level function.