关键词: Remote ischemic conditioning exosome microRNAs organ protection

Mesh : Exosomes / metabolism Animals Ischemic Preconditioning / methods Humans MicroRNAs / metabolism genetics blood Myocardial Reperfusion Injury / prevention & control metabolism

来  源:   DOI:10.1016/j.biopha.2024.117124

Abstract:
BACKGROUND: Remote ischemic conditioning (RIC) is considered a promising non-pharmacological therapeutic strategy to mitigate ischemic injury. Although the precise mechanisms of RIC\'s protective effects remain elusive, existing data suggest that exosomes contribute significantly to these processes through cell-to-cell communication OBJECTIVE: This review aims to elucidate the role of exosomes in RIC-mediated multi-organ protection.
METHODS: We systematically searched multiple databases through October 2023 for preclinical studies evaluating the effect of exosomes in ischemic models using RIC procedures. Key outcomes, such as improved organ function and reduced infarct size, were recorded. Articles were selected and data were extracted by independent pairs of reviewers.
RESULTS: A total of 16 relevant studies were identified in this review, showing that circulating exosomes derived from the plasma of RIC-treated animals exhibited protective effects akin to those of the RIC procedure itself. Exosome concentrations were measured in eight studies, six of which reported significant increases in the RIC group. Additional findings indicated that RIC might primarily modulate the expression of miRNAs and bioactive molecules delivered by exosomes, rather than directly altering circulating exosome levels. Notably, the expression of 11 distinct exosomal miRNAs was altered after RIC intervention, potentially involving multiple pathways.
CONCLUSIONS: Exosomes appear to play a pivotal role in the protective effects induced by RIC. Clarifying their function in RIC under different pathological situations represents a grand challenge for future research.
摘要:
背景:远程缺血预处理(RIC)被认为是减轻缺血性损伤的有希望的非药物治疗策略。虽然RIC的保护作用的确切机制仍然难以捉摸,现有数据表明,外泌体通过细胞间通讯对这些过程有重要贡献。目的:这篇综述旨在阐明外泌体在RIC介导的多器官保护中的作用。
方法:我们在2023年10月之前系统地检索了多个数据库,用于使用RIC程序评估外泌体在缺血模型中的作用的临床前研究。关键成果,如改善器官功能和减少梗死面积,被记录下来。由独立的审稿人选择文章并提取数据。
结果:本综述共确定了16项相关研究,表明来自RIC治疗动物血浆的循环外泌体表现出类似于RIC程序本身的保护作用。在八项研究中测量了外泌体浓度,其中6例报告RIC组显著增加.其他研究结果表明,RIC可能主要调节由外泌体递送的miRNAs和生物活性分子的表达,而不是直接改变循环外泌体水平。值得注意的是,RIC干预后,11个不同的外泌体miRNA的表达发生了改变,可能涉及多种途径。
结论:外泌体似乎在RIC诱导的保护作用中起关键作用。在不同的病理情况下明确它们在RIC中的功能是未来研究的巨大挑战。
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