p53-Upregulated Modulator of Apoptosis (PUMA)

As the leading cause of mortality in the United States, heart failure (HF) represents a disease state affected by a complex interplay between genetic, physiological, and environmental factors. Understanding the molecular mechanisms underlying the progression from normal cardiac function to ventricular dysfunction and overt HF will facilitate the identification of new therapeutic targets. Specifics of the underlying ultrastructural and molecular determinants of the progression to ventricular dysfunction and HF are still incompletely elucidated. The early adaptive response to increasing myocardial load and functional demand is characterized by cell hypertrophy and angiogenesis before pathological hypertrophy develops. A balance between compensatory hypertrophy and apoptotic pathways exists in the early stages of ventricular dysfunction, whereas upregulation of apoptotic pathways leading to myocyte damage and apoptosis as well as subsequent myocardial fibrosis is indicative of the progression to HF.1,2 There is evidence that apoptosis rates are increased in patients with HF,3 leading to the hypothesis that abrogation of apoptotic molecular pathways may be protective against the progression of disease.