Department of Pharmacy, Integral University, Lucknow, 226026, India.
Faculty of Pharmacy, Integral University, Lucknow, 226026, India.
Cardiovasc Toxicol. 2024 Nov;24(11):1268-1286. doi: 10.1007/s12012-024-09919-5. Epub 2024 Sep 6.
Cardiovascular disease is the deadly disease that can result in sudden death, and inflammation plays an important role in its onset and progression. High mobility group box 1 (HMGB1) is a nuclear protein that regulates transcription, DNA replication, repair, and nucleosome assembly. HMGB1 is released passively by necrotic tissues and actively secreted by stressed cells. Extracellular HMGB1 functions as a damage associated molecular patterns molecule, producing numerous redox forms that induce a range of cellular responses by binding to distinct receptors and interactors, including tissue inflammation and regeneration. Extracellular HMGB1 inhibition reduces inflammation and is protective in experimental models of myocardial ischemia/reperfusion damage, myocarditis, cardiomyopathies caused by mechanical stress, diabetes, bacterial infection, or chemotherapeutic drugs. HMGB1 administration following a myocardial infarction followed by permanent coronary artery ligation improves cardiac function by stimulating tissue regeneration. HMGB1 inhibits contractility and produces hypertrophy and death in cardiomyocytes, while also stimulating cardiac fibroblast activity and promoting cardiac stem cell proliferation and differentiation. Maintaining normal nuclear HMGB1 levels, interestingly, protects cardiomyocytes from apoptosis by limiting DNA oxidative stress, and mice with HMGB1cardiomyocyte-specific overexpression are partially protected from cardiac injury. Finally, elevated levels of circulating HMGB1 have been linked to human heart disease. As a result, following cardiac damage, HMGB1 elicits both detrimental and helpful responses, which may be due to the formation and stability of the various redox forms, the particular activities of which in this context are mostly unknown. This review covers recent findings in HMGB1 biology and cardiac dysfunction.
心血管疾病是一种致命的疾病，可导致猝死，炎症在其发病和进展中起着重要作用。高迁移率族蛋白 B1（HMGB1）是一种核蛋白，可调节转录、DNA 复制、修复和核小体组装。HMGB1 被动地从坏死组织中释放，主动地从应激细胞中分泌。细胞外 HMGB1 作为损伤相关分子模式分子发挥作用，产生多种氧化还原形式，通过与不同的受体和相互作用蛋白结合，诱导一系列细胞反应，包括组织炎症和再生。细胞外 HMGB1 抑制可减少炎症，并在心肌缺血/再灌注损伤、心肌炎、机械应激引起的心肌病、糖尿病、细菌感染或化学治疗药物的实验模型中具有保护作用。心肌梗死后行冠状动脉结扎术永久性结扎可通过刺激组织再生改善心功能。HMGB1 抑制收缩性并导致心肌细胞肥大和死亡，同时还刺激心肌成纤维细胞活性，促进心脏干细胞增殖和分化。有趣的是，维持正常核 HMGB1 水平可通过限制 DNA 氧化应激来保护心肌细胞免于凋亡，并且 HMGB1 心肌细胞特异性过表达的小鼠部分免受心脏损伤。最后，循环 HMGB1 水平升高与人类心脏病有关。因此，在心脏损伤后，HMGB1 引发有害和有益的反应，这可能是由于各种氧化还原形式的形成和稳定性所致，而这些形式在这种情况下的特定活性在很大程度上尚不清楚。这篇综述涵盖了 HMGB1 生物学和心脏功能障碍的最新发现。
