Myocyte hypertrophy and apoptosis: a balancing act.
In response to a variety of extrinsic and intrinsic stimuli that impose increased biomechanical stress the heart responds by enlarging the individual myofibers. Even though myocardial hypertrophy can normalize wall tension, it instigates an unfavorable outcome and threatens affected patients with sudden death or progression to overt heart failure, suggesting that in most instances hypertrophy is a maladaptive process. Increasing evidence suggests that several of the signaling cascades controlling myocyte growth in the adult heart also function to enhance survival of the myocyte population in response to pleiotropic death stimuli. In this review, we summarize recent insights into hypertrophic signaling pathways and their ability to control the balance between myocyte life and death. As modulation of myocardial growth by antagonizing intracellular signaling pathways is increasingly recognized as a potentially auspicious approach to prevent and treat heart failure, the design of such therapies should respect the dichotomous action of pathways that dictate a balance between myocyte hypertrophy, survival and death.
Hubrecht Laboratory and Interuniversity Cardiology Institute Netherlands, Royal Netherlands Academy of Arts and Sciences, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.
Vanessa P M
VP
van Empel
Leon J
LJ
De Windt
D000818:Animals; D017209:Apoptosis; D020013:Calcium Signaling / Q000502:physiology; D002311:Cardiomyopathy, Dilated / Q000378:metabolism / Q000473:pathology*; D016923:Cell Death; D048429:Cell Size; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D014409:Tumor Necrosis Factor-alpha