Quinn Maxwell, Zhang Richard Y K, Bello Idris, Rye Kerry-Anne, Thomas Shane R
Cardiometabolic Disease Research Group, School of Biomedical Sciences, Faculty of Medicine & Health, University of New South Wales, Sydney, NSW 2052, Australia.
Antioxidants (Basel). 2024 Jun 28;13(7):788. doi: 10.3390/antiox13070788.
Coronary artery disease (CAD) and myocardial infarction (MI) remain leading causes of death and disability worldwide. CAD begins with the formation of atherosclerotic plaques within the intimal layer of the coronary arteries, a process driven by persistent arterial inflammation and oxidation. Myeloperoxidase (MPO), a mammalian haem peroxidase enzyme primarily expressed within neutrophils and monocytes, has been increasingly recognised as a key pro-inflammatory and oxidative enzyme promoting the development of vulnerable coronary atherosclerotic plaques that are prone to rupture, and can precipitate a MI. Mounting evidence also implicates a pathogenic role for MPO in the inflammatory process that follows a MI, which is characterised by the rapid infiltration of activated neutrophils into the damaged myocardium and the release of MPO. Excessive and persistent cardiac inflammation impairs normal cardiac healing post-MI, resulting in adverse cardiac outcomes and poorer long-term cardiac function, and eventually heart failure. This review summarises the evidence for MPO as a significant oxidative enzyme contributing to the inappropriate inflammatory responses driving the progression of CAD and poor cardiac healing after a MI. It also details the proposed mechanisms underlying MPO's pathogenic actions and explores MPO as a novel therapeutic target for the treatment of unstable CAD and cardiac damage post-MI.
冠状动脉疾病（CAD）和心肌梗死（MI）仍然是全球范围内导致死亡和残疾的主要原因。CAD始于冠状动脉内膜层动脉粥样硬化斑块的形成，这一过程由持续性动脉炎症和氧化驱动。髓过氧化物酶（MPO）是一种主要在中性粒细胞和单核细胞中表达的哺乳动物血红素过氧化物酶，越来越被认为是一种关键的促炎和氧化酶，可促进易破裂的易损冠状动脉粥样硬化斑块的发展，并可引发心肌梗死。越来越多的证据还表明，MPO在心肌梗死后的炎症过程中起致病作用，其特征是活化的中性粒细胞迅速浸润到受损心肌中并释放MPO。过度和持续的心脏炎症会损害心肌梗死后的正常心脏愈合，导致不良的心脏结局和较差的长期心脏功能，最终导致心力衰竭。本综述总结了MPO作为一种重要的氧化酶的证据，该酶导致不适当的炎症反应，推动CAD的进展以及心肌梗死后心脏愈合不良。它还详细阐述了MPO致病作用的潜在机制，并探讨了MPO作为治疗不稳定CAD和心肌梗死后心脏损伤的新型治疗靶点。
