Changes in Cardiac Phenotype in Hypertrophy and Failure: From Receptor to Gene

摘要: The terminally differentiated adult cardiac myocyte cannot undergo cellular division. Growth of the heart in response to chronic hemodynamic overload therefore occurs through hypertrophy myocytes. adaptation during not only involves an increase cell size but also results a change phenotype modification pattern gene expression. From vitro studies, it can be learned that agonists like angiotensin-II, endothelin-1, cardiotrophin, basic fibroblast growth factor, insulin-like factor-I, or stimulation with α1 -adrenergic agonist phenylephrine induce hypertrophy. In vivo studies suggest especially angiotensin-II and endothelin-1 play aprominent role induction overload. These couple classical seven-transmembrane spanning domain (serpentine)receptors, signaling activation phosphoinositide pathway. This leads generation 1,2-diacylglycerol protein kinase C. Surprisingly, however, these were shown activate mitogen-activated (MAPK) pathway is typically activated by(growth factor) receptors harboring (intrinsic) tyrosine activity. Increased mechanical forces exerted on hypertrophy, partly autocrine paracrine factors such asangiotensin-II and/or endothelin-1. However, direct MAPK pathways by stretch might cross-talk integrin-focal adhesion Activated translocates nucleus, where phosphorylation processes are initiated lead altered transcription factor Some involved expression regulation hypertrophic have now been implied, knowledge concerning genetic cis-acting elements increasing. complexity interplay different (and possibly still unknown) do yet warrant complete picture regarding mechanism development