Novel molecular targets in the treatment of cardiac hypertrophy.
Left ventricular hypertrophy represents the heart's 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.
Luedde
Mark
M
Department of Internal Medicine III, University of Heidelberg, 69120 Heidelberg, Germany.
Katus
Hugo A
HA
Frey
Norbert
N
D000818:Animals; D019703:Calcineurin / Q000502:physiology; D006332:Cardiomegaly / Q000188:drug therapy* / Q000209:etiology*; D006152:Cyclic GMP / Q000502:physiology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000502:physiology; D004268:DNA-Binding Proteins; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology; D000071679:Glycogen Synthase Kinase 3 beta; D006655:Histone Deacetylases / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D020935:MAP Kinase Signaling System; D009124:Muscle Proteins / Q000502:physiology; D050778:NFATC Transcription Factors / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000502:physiology; D015398:Signal Transduction
D019703:Calcineurin; D006152:Cyclic GMP; D017869:Cyclic GMP-Dependent Protein Kinases; D004268:DNA-Binding Proteins; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D006655:Histone Deacetylases; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D050778:NFATC Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; D050796:STAT3 Transcription Factor; C108612:RCAN1 protein, human