Herrmann Joerg, Ciechanover Aaron, Lerman Lilach O, Lerman Amir
Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA.
Cardiovasc Res. 2004 Jan 1;61(1):11-21. doi: 10.1016/j.cardiores.2003.09.033.
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.
近年来，泛素-蛋白酶体系统已成为细胞内蛋白质非溶酶体降解的主要途径，涉及两个连续步骤。第一步，多个泛素部分共价结合到靶蛋白上，第二步由多酶蛋白酶体复合物识别并降解这些靶蛋白。除了清除受损和不需要的蛋白质外，该系统在调节各种生物途径中的细胞介质方面发挥着重要作用。最重要的是，这些生物途径包括炎症、细胞增殖和凋亡，所有这些都是动脉粥样硬化的重要特征。事实上，最近的实验证据支持泛素-蛋白酶体系统可能参与动脉粥样硬化的起始、进展和并发症阶段。这篇综述总结了关于泛素-蛋白酶体系统在心血管疾病中的最新发现，并讨论了蛋白酶体抑制剂在心血管治疗中的潜在用途。
