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靶向抑制 STAT3 作为动脉粥样硬化潜在的治疗策略。

Targeted inhibition of STAT3 as a potential treatment strategy for atherosclerosis.

机构信息

Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education. Faculty of Life Sciences, Northwest University, 229 Taibai North Road, Xi'an 710069, China.

School of Basic Medicine, The Fourth Military Medical University, 169 Changle West Road, Xi'an 710032, China.

出版信息

Theranostics. 2019 Aug 14;9(22):6424-6442. doi: 10.7150/thno.35528. eCollection 2019.

Abstract

Atherosclerosis is the main pathological basis of ischemic cardiovascular and cerebrovascular diseases and has attracted more attention in recent years. Multiple studies have demonstrated that the signal transducer and activator of transcription 3 (STAT3) plays essential roles in the process of atherosclerosis. Moreover, aberrant STAT3 activation has been shown to contribute to the occurrence and development of atherosclerosis. Therefore, the study of STAT3 inhibitors has gradually become a focal research topic. In this review, we describe the crucial roles of STAT3 in endothelial cell dysfunction, macrophage polarization, inflammation, and immunity during atherosclerosis. STAT3 in mitochondria is mentioned as well. Then, we present a summary and classification of STAT3 inhibitors, which could offer potential treatment strategies for atherosclerosis. Furthermore, we enumerate some of the problems that have interfered with the development of mature therapies utilizing STAT3 inhibitors to treat atherosclerosis. Finally, we propose ideas that may help to solve these problems to some extent. Collectively, this review may be useful for developing future STAT3 inhibitor therapies for atherosclerosis.

摘要

动脉粥样硬化是缺血性心脑血管疾病的主要病理学基础,近年来受到了更多关注。多项研究表明,信号转导子和转录激活子 3(STAT3)在动脉粥样硬化过程中发挥着重要作用。此外,异常的 STAT3 激活被认为有助于动脉粥样硬化的发生和发展。因此,STAT3 抑制剂的研究逐渐成为一个焦点研究课题。在这篇综述中,我们描述了 STAT3 在动脉粥样硬化过程中内皮细胞功能障碍、巨噬细胞极化、炎症和免疫中的关键作用。还提到了 STAT3 在线粒体中的作用。然后,我们对 STAT3 抑制剂进行了总结和分类,这为动脉粥样硬化的治疗提供了潜在的治疗策略。此外,我们列举了一些干扰利用 STAT3 抑制剂治疗动脉粥样硬化的成熟疗法发展的问题。最后,我们提出了一些可能有助于在一定程度上解决这些问题的想法。总的来说,这篇综述可能有助于开发未来针对动脉粥样硬化的 STAT3 抑制剂疗法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5cab/6771242/9a2c161907ec/thnov09p6424g001.jpg

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