Department of Neurorehabilitation Sciences, Casa Cura Policlinico (CCP), Milan, Italy.
Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Pharmacol Ther. 2019 Apr;196:160-182. doi: 10.1016/j.pharmthera.2018.12.005. Epub 2018 Dec 6.
High-mobility group box 1 (HMGB1) is one of the most abundant proteins in eukaryotes and the best characterized damage-associated molecular pattern (DAMP). The biological activities of HMGB1 depend on its subcellular location, context and post-translational modifications. Inside the nucleus, HMGB1 is engaged in many DNA events such as DNA repair, transcription regulation and genome stability; in the cytoplasm, its main function is to regulate the autophagic flux while in the extracellular environment, it possesses more complicated functions and it is involved in a large variety of different processes such as inflammation, migration, invasion, proliferation, differentiation and tissue regeneration. Due to this pleiotropy, the role of HMGB1 has been vastly investigated in various pathological diseases and a large number of studies have explored its function in cardiovascular pathologies. However, in this contest, the precise mechanism of action of HMGB1 and its therapeutic potential are still very controversial since is debated whether HMGB1 is involved in tissue damage or plays a role in tissue repair and regeneration. The main focus of this review is to provide an overview of the effects of HMGB1 in different ischemic heart diseases and to discuss its functions in these pathological conditions.
高迁移率族蛋白 B1（HMGB1）是真核生物中含量最丰富的蛋白质之一，也是研究最深入的损伤相关分子模式（DAMP）之一。HMGB1 的生物学活性取决于其亚细胞位置、上下文和翻译后修饰。在细胞核内，HMGB1 参与许多 DNA 事件，如 DNA 修复、转录调控和基因组稳定性；在细胞质中，其主要功能是调节自噬流；而在细胞外环境中，它具有更复杂的功能，并参与多种不同的过程，如炎症、迁移、侵袭、增殖、分化和组织再生。由于这种多效性，HMGB1 在各种病理疾病中的作用已经被广泛研究，大量研究探索了其在心血管病理中的功能。然而，在这种情况下，HMGB1 的精确作用机制及其治疗潜力仍存在很大争议，因为人们争论的焦点是 HMGB1 是否参与组织损伤，还是在组织修复和再生中发挥作用。本文综述的主要重点是概述 HMGB1 在不同缺血性心脏病中的作用，并讨论其在这些病理条件下的功能。
