title: Regulatory roles of the ubiquitin-proteasome system in cardiomyocyte apoptosis.
abstract: Cardiovascular disease is the leading cause of death in the western world. The major contributor of all cardiovascular deaths is myocardial infarction, which often progresses into end-stage heart failure. The loss of cardiomyocytes is a key problem in the development of cardiovascular disease. Two main processes mediate cardiomyocyte loss: necrosis and apoptosis. In contrast to necrosis, apoptosis is a well regulated process essential in normal development and tissue homeostasis. Tight regulation of this process is crucial, especially in post mitotic cells lacking regenerative capacity, like cardiomyocytes. The ubiquitin-proteasome system, accounting for 80 to 90% of intracellular protein degradation, appears to be involved in the regulation of apoptosis. In this process, regulation is performed through the degradation of pro- and anti-apoptotic proteins involved in cell cycle control and specific apoptotic pathways. On the one hand, disturbances in this normally well regulated process are associated with a number of cardiovascular diseases. On the other hand, proteasomal dysfunction may result from ischemia, hypertrophy and heart failure, and a number of cardiomyopathies. This paper reviews the current knowledge on the role of the ubiquitin-proteasome system-mediated regulation of cardiomyocyte apoptosis in cardiovascular disease. Finally, within the ubiquitin-proteasome system new molecular targets for treatment of cardiovascular disease are suggested.
authors.affiliation: Department of Medical Physiology, Division Heart & Lungs, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: W
authors.initials: W
authors.lastname: Sohns
authors.forename: T A B
authors.initials: TA
authors.lastname: van Veen
authors.forename: M A G
authors.initials: MA
authors.lastname: van der Heyden
mesh_terms: D000818:Animals; D017209:Apoptosis; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D046988:Proteasome Endopeptidase Complex / Q000502:physiology*; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex