Cardiovascular Research 2004 61(1):11-21; doi:10.1016/j.cardiores.2003.09.033
© 2004 by European Society of Cardiology
Copyright © 2004, European Society of Cardiology
The ubiquitin–proteasome system in cardiovascular diseases—a hypothesis extended
aDivision of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA
bRappaport Institute for Research in Medical Sciences, Technion-Israel Institue of Technology, Haifa, Israel
cDivision of Hypertension, Mayo Clinic, Rochester, MN, USA
* Corresponding author. Department of Internal Medicine, Mayo Clinic Rochester, 200 First Street SW, Rochester, MN 55905, USA. Tel.: +1-507-255-5890; fax: +1-507-255-1824. herrmann.joerg{at}mayo.edu
During recent years, the ubiquitin–proteasome system has become known as the major pathway of non-lysosomal degradation of intracellular proteins, involving two sequential steps. In the first step, multiple moieties of ubiquitin are covalently bound to target proteins to be recognized and degraded by the multi-enzymatic proteasome complex in the second step. In addition to the elimination of damaged and unneeded proteins, this system fulfills an important function in the regulation of cellular mediators in various biological pathways. Foremost, these biological pathways include inflammation, cell proliferation, and apoptosis, all of which constitute important characteristics of atherosclerosis. Indeed, recent experimental evidence supports a potential involvement of the ubiquitin–proteasome system in the initiation, progression, and complication stage of atherogenesis. This review summarizes recent findings regarding the ubiquitin–proteasome system in cardiovascular diseases and discusses the potential use of proteasome inhibitors in cardiovascular therapy.
KEYWORDS Apoptosis; Atherosclerosis; Coronary disease; Restenosis
Time for primary review 29 days
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