Left ventricular hypertrophy represents the hearts response to increased biomechanical stress such as arterial hypertension or valvular heart disease. Cardiac hypertrophy has traditionally been considered a compensatory mechanism required to normalize wall tension and to maintain cardiac output. However, recent clinical studies as well as several animal models have shown that sustained cardiac hypertrophy is rather a maladaptive process, ultimately leading to heart failure and sudden death independent of the underlying cause of hypertrophy. Throughout the past decade, much effort has thus been spent on deciphering the molecular signaling pathways mediating cardiac growth. Identification of novel molecules regulating cardiac hypertrophy could offer the basis for a new generation of cardiovascular drugs. In this review we focus on recent insights into hypertrophic signaling and consider current and emerging approaches to inhibit hypertrophy with the ultimate goal to prevent or delay the onset of heart failure and sudden death in patients.
Hypertrophy, calcineurin, Cyclic GMP/PKG-1, phosphoinositide 3-kinase, Akt, glycogen synthase kinase-3, myocyte-enhancer factor 2, histone deacetylases, Gq/G11, small G proteins, MAPK, GP130, Na/H exchanger
Department of InternalMedicine III, University of Heidelberg, Im Neuenheimer Feld 410, 69120Heidelberg, Germany.