Gu Chengying, Chen Qian, Wang Liang, Qian Hao, Tian Ran, Liu Zhenyu, Zhang Shuyang
Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Eur J Pharmacol. 2025 Sep 5;1002:177855. doi: 10.1016/j.ejphar.2025.177855. Epub 2025 Jun 20.
Platelet activation is a key factor that aggravates the prognosis of myocardial ischemia-reperfusion injury (MIRI). Peroxiredoxin 2 (Prdx2) is an endogenous peroxidase that helps mitigate atherosclerosis and myocardial infarction; however, its effect on platelets in MIRI remains unclear.
Prdx2 expression and platelet activation status were assessed in patients with acute coronary syndrome (ACS) and stable angina pectoris (SAP). Then, the effect of Prdx2 on agonist-induced platelet activation and MIRI was assessed by using the rat MIRI model. SC79 (an AKT pathway activator) was used to reveal the underlying mechanisms.
Patients with ACS had lower serum Prdx2 levels than those with SAP. Rats pretreated with Prdx2 exhibited reduced levels of creatine kinase-myocardial band (CK-MB) and lactate dehydrogenase (LDH). HE staining revealed that Prdx2 alleviated myocardial necrosis and inflammatory infiltration in MIRI rats. Prdx2-pretreated rats revealed improved cardiac systolic function compared to the sham controls. 2,3,5-triphenyltetrazolium chloride staining demonstrated that the MIRI was attenuated by Prdx2 pretreatment. When compared to sham controls, Prdx2 pretreatment platelets exhibited inhibition in platelet aggregation, Adenosine Triphosphate (ATP) release, P-selectin and αIIbβ3 expression, spreading area on fibrinogen, and in vivo hemostatic function. SC79 partially attenuated the above-mentioned platelet inhibition and cardioprotection of Prdx2. Protein blotting experiments of platelets revealed that Prdx2 inhibited AKT/NF-κB phosphorylation in MIRI, which SC79 reversed.
Prdx2 inhibited platelet activation and ameliorated MIRI by inhibiting AKT/NF-κB phosphorylation in platelets.
血小板活化是加重心肌缺血再灌注损伤（MIRI）预后的关键因素。过氧化物酶2（Prdx2）是一种内源性过氧化物酶，有助于减轻动脉粥样硬化和心肌梗死；然而，其在MIRI中对血小板的作用仍不清楚。
评估急性冠状动脉综合征（ACS）和稳定型心绞痛（SAP）患者的Prdx2表达和血小板活化状态。然后，通过大鼠MIRI模型评估Prdx2对激动剂诱导的血小板活化和MIRI的影响。使用SC79（一种AKT通路激活剂）来揭示潜在机制。
ACS患者的血清Prdx2水平低于SAP患者。用Prdx2预处理的大鼠肌酸激酶同工酶（CK-MB）和乳酸脱氢酶（LDH）水平降低。苏木精-伊红染色显示，Prdx2减轻了MIRI大鼠的心肌坏死和炎症浸润。与假手术对照组相比，Prdx2预处理的大鼠心脏收缩功能得到改善。氯化三苯基四氮唑染色表明，Prdx2预处理减轻了MIRI。与假手术对照组相比，Prdx2预处理的血小板在血小板聚集、三磷酸腺苷（ATP）释放、P-选择素和αIIbβ3表达、在纤维蛋白原上的铺展面积以及体内止血功能方面表现出抑制作用。SC79部分减弱了Prdx2对上述血小板的抑制作用和心脏保护作用。血小板的蛋白质印迹实验表明，Prdx2在MIRI中抑制AKT/NF-κB磷酸化，而SC79可逆转这种抑制作用。
Prdx2通过抑制血小板中的AKT/NF-κB磷酸化来抑制血小板活化并改善MIRI。
