Altered coronary artery function, arteriogenesis and endothelial YAP signaling in postnatal hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a cardiovascular genetic disease caused largely by sarcomere protein mutations. Gaps in our understanding exist as to how maladaptive sarcomeric biophysical signals are transduced to intra- and extracellular compartments leading to HCM progression. To investigate early HCM progression, we focused on the onset of myofilament dysfunction during neonatal development and examined cardiac dynamics, coronary vascular structure and function, and mechano-transduction signaling in mice harboring a thin-filament HCM mutation.

Coronary arterial vasculature in the pathophysiology of hypertrophic cardiomyopathy.

Alterations in the coronary vascular system are likely associated with a mismatch between energy demand and energy supply and critical in triggering the cascade of events that leads to symptomatic hypertrophic cardiomyopathy. Targeting the early events, particularly vascular remodeling, may be a key approach to developing effective treatments. Improvement in our understanding of hypertrophic cardiomyopathy began with the results of early biophysical studies, proceeded to genetic analyses pinpointing the mutational origin, and now pertains to imaging of the metabolic and flow-related consequences of such mutations.