De Bartolo Anna, Romeo Naomi, Angelone Tommaso, Rocca Carmine
Cellular and Molecular Cardiovascular Physiology and Pathophysiology Laboratory, Department of Biology, E. And E. S. (DiBEST), University of Calabria, Cosenza, Italy.
National Institute of Cardiovascular Research (INRC), Bologna, Italy.
Acta Physiol (Oxf). 2025 Jul;241(7):e70062. doi: 10.1111/apha.70062.
Timely myocardial reperfusion is essential for restoring blood flow to post-ischemic tissue, thereby reducing cardiac injury and limiting infarct size. However, this process can paradoxically result in additional, irreversible myocardial damage, known as myocardial ischemia-reperfusion injury (MIRI). The goal of this review is to explore the role of specialized pro-resolving mediators (SPMs) in atherosclerosis and MIRI, and to assess the therapeutic potential of targeting inflammation resolution in these cardiovascular conditions.
This review summarizes current preclinical and clinical evidence on the involvement of SPMs in the pathogenesis of atherosclerosis and MIRI, acknowledging that several cellular and molecular aspects of their mechanisms of action remain to be fully elucidated.
MIRI is a complex phenomenon in which inflammation, initially triggered during ischemia and further amplified upon reperfusion, plays a central role in its pathogenesis. Various cellular and molecular players mediate the initial pro-inflammatory response and the subsequent anti-inflammatory reparative phase following acute myocardial infarction (AMI), contributing both to ischemia- and reperfusion-induced damage as well as to the healing process. SPMs have emerged as key endogenous immunoresolvents with potent anti-inflammatory, antioxidant, and pro-resolving properties that contribute to limit excessive acute inflammation and promote tissue repair. While dysregulated SPM-related signaling has been linked to various cardiovascular diseases (CVD), their precise role in AMI and MIRI remains incompletely understood.
Targeting inflammation resolution may represent a promising therapeutic strategy for mitigating atheroprogression and addressing a complex condition such as MIRI.
及时进行心肌再灌注对于恢复缺血后组织的血流至关重要,从而减少心脏损伤并限制梗死面积。然而,这一过程可能反常地导致额外的、不可逆的心肌损伤,即心肌缺血再灌注损伤(MIRI)。本综述的目的是探讨特异性促消退介质(SPMs)在动脉粥样硬化和MIRI中的作用,并评估在这些心血管疾病中靶向炎症消退的治疗潜力。
本综述总结了目前关于SPMs参与动脉粥样硬化和MIRI发病机制的临床前和临床证据,同时承认其作用机制的几个细胞和分子方面仍有待充分阐明。
MIRI是一种复杂的现象,其中炎症在缺血期间最初触发,并在再灌注时进一步放大,在其发病机制中起核心作用。各种细胞和分子因素介导急性心肌梗死(AMI)后的初始促炎反应和随后的抗炎修复阶段,既导致缺血和再灌注诱导的损伤,也促进愈合过程。SPMs已成为关键的内源性免疫消退剂,具有强大的抗炎、抗氧化和促消退特性,有助于限制过度的急性炎症并促进组织修复。虽然与SPM相关的信号失调与各种心血管疾病(CVD)有关,但其在AMI和MIRI中的精确作用仍不完全清楚。
靶向炎症消退可能是减轻动脉粥样硬化进展和应对诸如MIRI等复杂病症的一种有前景的治疗策略。