Tian Xiao Yu, Ma Shuangtao, Tse Gary, Wong Wing Tak, Huang Yu
School of Biomedical Sciences, Institute of Vascular Medicine, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
Division of Nanomedicine and Molecular Intervention, Department of Medicine, Michigan State University, East Lansing, MI, United States.
Front Physiol. 2018 Aug 2;9:1060. doi: 10.3389/fphys.2018.01060. eCollection 2018.
Uncoupling protein 2 (UCP2) belongs to the family of mitochondrial anion carrier proteins. It uncouples oxygen consumption from ATP synthesis. UCP2 is ubiquitously expressed in most cell types to reduce oxidative stress. It is tightly regulated at the transcriptional, translational, and post-translational levels. UCP2 in the cardiovascular system is being increasingly recognized as an important molecule to defend against various stress signals such as oxidative stress in the pathology of vascular dysfunction, atherosclerosis, hypertension, and cardiac injuries. UCP2 protects against cellular dysfunction through reducing mitochondrial oxidative stress and modulation of mitochondrial function. In view of the different functions of UCP2 in various cell types that contribute to whole body homeostasis, cell type-specific modification of UCP2 expression may offer a better approach to help understanding how UCP2 governs mitochondrial function, reactive oxygen species production and transmembrane proton leak and how dysfunction of UCP2 participates in the development of cardiovascular diseases. This review article provided an update on the physiological regulation of UCP2 in the cardiovascular system, and also discussed the involvement of UCP2 deficiency and associated oxidative stress in the pathogenesis of several common cardiovascular diseases. Drugs targeting UCP2 expression and activity might serve another effective strategy to ameliorate cardiovascular dysfunction. However, more detailed mechanistic study will be needed to dissect the role of UCP2, the regulation of UCP2 expression, and the cellular responses to the changes of UCP2 expression in normal and stressed situations at different stages of cardiovascular diseases.
解偶联蛋白2（UCP2）属于线粒体阴离子载体蛋白家族。它使氧消耗与ATP合成解偶联。UCP2在大多数细胞类型中广泛表达以减轻氧化应激。它在转录、翻译和翻译后水平受到严格调控。心血管系统中的UCP2越来越被认为是一种重要分子，可抵御各种应激信号，如血管功能障碍、动脉粥样硬化、高血压和心脏损伤病理过程中的氧化应激。UCP2通过减轻线粒体氧化应激和调节线粒体功能来保护细胞功能。鉴于UCP2在有助于全身稳态的各种细胞类型中的不同功能，对UCP2表达进行细胞类型特异性修饰可能提供一种更好的方法，以帮助理解UCP2如何控制线粒体功能、活性氧产生和跨膜质子泄漏，以及UCP2功能障碍如何参与心血管疾病的发生发展。这篇综述文章提供了心血管系统中UCP2生理调节的最新情况，并讨论了UCP2缺乏和相关氧化应激在几种常见心血管疾病发病机制中的作用。靶向UCP2表达和活性的药物可能是改善心血管功能障碍的另一种有效策略。然而，需要更详细的机制研究来剖析UCP2的作用、UCP2表达的调控以及在心血管疾病不同阶段正常和应激情况下细胞对UCP2表达变化的反应。
