Hume Robert D, Chong James J H
Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, 176 Hawkesbury Rd, Westmead, NSW 2145, Australia.
Centre for Heart Research, Westmead Institute for Medical Research, The University of Sydney, 176 Hawkesbury Rd, Westmead, NSW 2145, Australia; Department of Cardiology, Westmead Hospital, Hawkesbury Rd, Westmead, NSW 2145, Australia.
Clin Ther. 2020 Oct;42(10):1923-1943. doi: 10.1016/j.clinthera.2020.09.006. Epub 2020 Oct 1.
Despite modern reperfusion and pharmacologic therapies, myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide. Therefore, the development of further therapeutics affecting post-MI recovery poses significant benefits. This review focuses on the post-MI immune response and immunomodulatory therapeutics that could improve the wound-healing response.
This narrative review used OVID versions of MEDLINE and EMBASE searching for clinical therapeutics targeting the immune system during MI. Preclinical models and clinical trials were included. Additional studies were sourced from the reference lists of relevant articles and other personal files.
After MI, cardiomyocytes are starved of oxygen and undergo cell death via coagulative necrosis. This process activates the immune system and a multifaceted wound-healing response, comprising a number of complex and overlapping phases. Overactivation or persistence of one or more of these phases can have potentially lethal implications. This review describes the immune response post-MI and any adverse events that can occur during these different phases. Second, we describe immunomodulatory therapies that attempt to target these immune cell aberrations by mitigating or diminishing their effects on the wound-healing response. Also discussed are adult stem/progenitor cell therapies, exosomes, and regulatory T cells, and their immunomodulatory effects in the post-MI setting.
An updated understanding into the importance of various inflammatory cell phenotypes, coupled with new technologies, may hold promise for a new era of immunomodulatory therapeutics. The implications of such therapies could dramatically improve patients' quality of life post-MI and reduce the incidence of progressive heart failure.
尽管有现代再灌注和药物治疗，但心肌梗死（MI）仍是全球发病和死亡的主要原因。因此，开发影响心肌梗死后恢复的进一步治疗方法具有重大益处。本综述聚焦于心肌梗死后的免疫反应以及可改善伤口愈合反应的免疫调节疗法。
本叙述性综述使用OVID版的MEDLINE和EMBASE检索针对心肌梗死期间免疫系统的临床治疗方法。纳入了临床前模型和临床试验。其他研究来自相关文章的参考文献列表和其他个人文件。
心肌梗死后，心肌细胞缺氧并通过凝固性坏死发生细胞死亡。这一过程激活免疫系统和多方面的伤口愈合反应，包括多个复杂且相互重叠的阶段。这些阶段中一个或多个阶段的过度激活或持续存在可能具有潜在的致命影响。本综述描述了心肌梗死后的免疫反应以及在这些不同阶段可能发生的任何不良事件。其次，我们描述了试图通过减轻或减少其对伤口愈合反应的影响来针对这些免疫细胞异常的免疫调节疗法。还讨论了成体干细胞/祖细胞疗法、外泌体和调节性T细胞，以及它们在心肌梗死后环境中的免疫调节作用。
对各种炎症细胞表型重要性的最新认识，再加上新技术，可能为免疫调节治疗的新时代带来希望。此类疗法的意义可能会显著改善心肌梗死后患者的生活质量，并降低进行性心力衰竭的发生率。
