Sumanth D. Prabhu, MD
Year elected: 2009
Current membership category: Senior
Professor and Chief, Division of CardiologyWashington University School of Medicine
660 S. Euclid Avenue
St. Louis, MO 63110
United States of America
Research in the Prabhu laboratory focuses on the mechanisms of ventricular dysfunction and pathological remodeling in heart failure, and emphasizes the use of integrative physiological approaches in small and large animal models. One central theme is the effect of inflammatory activation and oxidative stress in the failing heart. Our work has demonstrated that chronic β-adrenergic receptor activation induces inflammatory cytokines in the heart, and that amelioration of inflammation plays an important role in the therapeutic benefits of β-adrenergic blockade in heart failure. Also, an important mechanism of oxidative stress induced by chronic β-adrenergic receptor stimulation in the heart is the transcriptional repression of Cu/Zn superoxide dismutase via the β1-receptor, an effect distinct from augmentation of free radical production. More recently, we have shown that tumor necrosis factor (TNF) has divergent receptor-specific effects in the failing heart. Specifically, signaling via TNF receptor-1 exacerbates cardiac hypertrophy, NF-kappaB activation and inflammation, and augments myocardial apoptosis, whereas signaling via TNF receptor-2 ameliorates these events, suggesting that consideration of TNF receptor-specific effects is paramount when developing therapeutic anti-TNF strategies in heart failure. We have also extended this theme in a different direction, having shown that environmental exposure to aldehyde pollutants induces cardiac dysfunction, chronic inflammation, TNF expression and cardiomyopathy, raising the concept of an environmental basis for idiopathic dilated cardiomyopathy. Current studies using chimeric mice are focusing on the role of the inflammatory cell in pathological remodeling and the effects of inducible nitric oxide synthase (iNOS) and TNF receptor-specific signaling in macrophages in heart failure.
Deborah J. Veis, MD, PhD is the representative at this institution.
University of Louisville School of Medicine (Tertiary)