title: Controlling cardiomyocyte survival.
abstract: Gradually the distinction between signalling pathways originally believed to be specific for either hypertrophy, cell cycle control, apoptosis and cell survival are fading. The subtle variations in stimuli to a cell and the microenvironment will determine cell fate. In cardiomyocytes the entrance into the cell cycle is efficiently blocked. Therefore attention has focused on pathways involved in hypertrophy to assess effects in ischaemic models and vice versa. Interventions at different levels have been shown to be cardiomyocyte protective. Various growth factors (including IGF1 and FGF1,2) have shown to prevent or delay cardiomyocyte loss in and ex vivo. Similar results have been reported for downstream interventions in the signalling pathways. Strong effects after MAPK activation have been shown in gene targeted mice. Especially constitutive activation of the ERK proteins prevents ischemic damage of the heart with conservation of left ventricular function. Evidence for a key role of nuclear Akt in preventing apoptosis is accumulating from various genetic and pharmacological sources. Development of techniques to measure the level of cardiomyocyte death depends on further improvements in molecular imaging in mouse and human. In addition to studying cardiomyocyte cell death, it is crucial to measure myocardial function. Whether hypertrophy following ischaemia is adaptive or maladaptive and whether all apoptosis is detrimental will have to be determined by assessment of left ventricular function through invasive and noninvasive methods.
authors.affiliation: Department of Cardiology, Heart Lung Center Utrecht, UMC Utrecht, The Netherlands.
authors.forename: Nicolaas
authors.initials: N
authors.lastname: de Jonge
authors.forename: Marie Jose
authors.initials: MJ
authors.lastname: Goumans
authors.forename: Daan
authors.initials: D
authors.lastname: Lips
authors.forename: Rutger
authors.initials: R
authors.lastname: Hassink
authors.forename: Eva J
authors.initials: EJ
authors.lastname: Vlug
authors.forename: Roy
authors.initials: R
authors.lastname: van der Meel
authors.forename: Christopher Donald
authors.initials: CD
authors.lastname: Emmerson
authors.forename: Joppe
authors.initials: J
authors.lastname: Nijman
authors.forename: Leon
authors.initials: L
authors.lastname: de Windt
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
mesh_terms: D000818:Animals; D017209:Apoptosis; D002470:Cell Survival; D006331:Heart Diseases / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008024:Ligands; D051379:Mice; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000473:pathology*; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D008024:Ligands