Abstract 11890: Defining the Role of p62 in Cardiac Hypertrophy and Pathology

Introduction: Accumulation of ubiquitinated proteins and aggregates are increasingly being recognized as playing major roles in cardiac disease and heart failure. Recent work suggests that a protein named p62 plays a regulatory role in the accumulation of ubiquitinated proteins and protein aggregates. Chronic hemodynamic stress causes cardiac hypertrophy and triggers a concomitant increase in p62 and ubiquitinated protein levels. Hypothesis: p62 expression contributes to proteotoxic accumulation and cardiac hypertrophy. Methods: An adenovirus was created to drive p62 expression in neonatal cardiomyocytes to study role of p62 in cardiac cell growth and proteotoxic accumulation. Trans-aortic constriction or sham surgeries were performed on wild-type and p62-deficient mice to test if p62 was necessary for pressure-overload induced hypertrophy and pathology. Results: Overexpression of p62 in cardiomyocytes significantly increased cardiomyocyte size and caused a corresponding increase in aggregate accumulation...