Department of Molecular Biomedical Sciences and Comparative Medicine Institute, North Carolina State University, Raleigh, NC 27607, USA.
Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA.
Sci Adv. 2020 Feb 5;6(6):eaay0589. doi: 10.1126/sciadv.aay0589. eCollection 2020 Feb.
An acute myocardial infarction (AMI) induces a sterile inflammatory response that facilitates further heart injury and promotes adverse cardiac remodeling. Interleukin-1β (IL-1β) plays a central role in the sterile inflammatory response that results from AMI. Thus, IL-1β blockage is a promising strategy for treatment of AMI. However, conventional IL-1β blockers lack targeting specificity. This increases the risk of serious side effects. To address this problem herein, we fabricated platelet microparticles (PMs) armed with anti-IL-1β antibodies to neutralize IL-1β after AMI and to prevent adverse cardiac remodeling. Our results indicate that the infarct-targeting PMs could bind to the injured heart, increasing the number of anti-IL-1β antibodies therein. The anti-IL-1β platelet PMs (IL1-PMs) protect the cardiomyocytes from apoptosis by neutralizing IL-1β and decreasing IL-1β-driven caspase-3 activity. Our findings indicate that IL1-PM is a promising cardiac detoxification agent that removes cytotoxic IL-1β during AMI and induces therapeutic cardiac repair.
急性心肌梗死(AMI)会引发无菌性炎症反应,从而进一步损害心脏并促进不良的心脏重构。白细胞介素-1β(IL-1β)在 AMI 引起的无菌性炎症反应中发挥核心作用。因此,IL-1β 阻断是治疗 AMI 的一种有前途的策略。然而,传统的 IL-1β 阻滞剂缺乏靶向特异性。这增加了发生严重副作用的风险。为了解决这个问题,我们制备了带有抗 IL-1β 抗体的血小板微粒(PMs),以在 AMI 后中和 IL-1β 并防止不良的心脏重构。我们的结果表明,梗死靶向 PMs 可以与受损的心脏结合,增加其中的抗 IL-1β 抗体数量。抗 IL-1β 血小板 PMs(IL1-PMs)通过中和 IL-1β 和降低 IL-1β 驱动的 caspase-3 活性来保护心肌细胞免于凋亡。我们的研究结果表明,IL1-PM 是一种有前途的心脏解毒剂,可在 AMI 期间清除细胞毒性的 IL-1β 并诱导治疗性心脏修复。