NPPA and cardiac hypertrophy: During pressure overload, APN deficiency accelerated the transition from cardiac hypertrophy to heart failure20 and cardiac fibrosis36, but pretreatment with recombinant APN significantly decreased H2O2-induced cardiomyocyte hypertrophy by decreasing total protein levels, protein synthesis, and atrial natriuretic factor and brain natriuretic peptide expression36.