Institut de Génomique Fonctionnelle, Université de Montpellier, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Montpellier, France.
LabEx Ion Channel Science and Therapeutics, Université de Nice, Nice, France.
Physiol Rev. 2024 Apr 1;104(2):659-725. doi: 10.1152/physrev.00009.2023. Epub 2023 Aug 17.
Acute myocardial infarction (AMI) is the leading cause of cardiovascular death and remains the most common cause of heart failure. Reopening of the occluded artery, i.e., reperfusion, is the only way to save the myocardium. However, the expected benefits of reducing infarct size are disappointing due to the reperfusion paradox, which also induces specific cell death. These ischemia-reperfusion (I/R) lesions can account for up to 50% of final infarct size, a major determinant for both mortality and the risk of heart failure (morbidity). In this review, we provide a detailed description of the cell death and inflammation mechanisms as features of I/R injury and cardioprotective strategies such as ischemic postconditioning as well as their underlying mechanisms. Due to their biological properties, the use of mesenchymal stromal/stem cells (MSCs) has been considered a potential therapeutic approach in AMI. Despite promising results and evidence of safety in preclinical studies using MSCs, the effects reported in clinical trials are not conclusive and even inconsistent. These discrepancies were attributed to many parameters such as donor age, in vitro culture, and storage time as well as injection time window after AMI, which alter MSC therapeutic properties. In the context of AMI, future directions will be to generate MSCs with enhanced properties to limit cell death in myocardial tissue and thereby reduce infarct size and improve the healing phase to increase postinfarct myocardial performance.
急性心肌梗死（AMI）是心血管死亡的主要原因，也是心力衰竭最常见的原因。闭塞动脉的再通，即再灌注，是挽救心肌的唯一方法。然而，由于再灌注悖论，即再灌注也会诱导特定的细胞死亡，预期的减少梗死面积的益处令人失望。这些缺血再灌注（I/R）损伤可达最终梗死面积的 50%，是死亡率和心力衰竭（发病率）风险的主要决定因素。在这篇综述中，我们详细描述了细胞死亡和炎症机制作为 I/R 损伤的特征，以及缺血后处理等心脏保护策略及其潜在机制。由于其生物学特性，间充质基质/干细胞（MSCs）的应用被认为是 AMI 的一种潜在治疗方法。尽管在使用 MSCs 的临床前研究中取得了有希望的结果和安全性证据，但临床试验报告的效果并不确定，甚至相互矛盾。这些差异归因于许多参数，如供体年龄、体外培养和储存时间以及 AMI 后注射时间窗，这些参数改变了 MSC 的治疗特性。在 AMI 的背景下，未来的方向将是生成具有增强特性的 MSCs，以限制心肌组织中的细胞死亡，从而减少梗死面积，并改善愈合阶段，以提高梗死后心肌的性能。
