The ubiquitin-proteasome system and cardiovascular disease.
Over the past decade, the role of the ubiquitin-proteasome system (UPS) has been the subject of numerous studies to elucidate its role in cardiovascular physiology and pathophysiology. There have been many advances in this field including the use of proteomics to achieve a better understanding of how the cardiac proteasome is regulated. Moreover, improved methods for the assessment of UPS function and the development of genetic models to study the role of the UPS have led to the realization that often the function of this system deviates from the norm in many cardiovascular pathologies. Hence, dysfunction has been described in atherosclerosis, familial cardiac proteinopathies, idiopathic dilated cardiomyopathies, and myocardial ischemia. This has led to numerous studies of the ubiquitin protein (E3) ligases and their roles in cardiac physiology and pathophysiology. This has also led to the controversial proposition of treating atherosclerosis, cardiac hypertrophy, and myocardial ischemia with proteasome inhibitors. Furthering our knowledge of this system may help in the development of new UPS-based therapeutic modalities for mitigation of cardiovascular disease.
Center for Heart and Lung Research, The Feinstein Institute for Medical Research, Manhasset, New York, USA.
Saul R
SR
Powell
Joerg
J
Herrmann
Amir
A
Lerman
Cam
C
Patterson
Xuejun
X
Wang
D002318:Cardiovascular Diseases / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D008955:Models, Cardiovascular; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
D061988:Proteasome Inhibitors; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; D046988:Proteasome Endopeptidase Complex