Peroxiredoxin 2 alleviates myocardial ischemia-reperfusion injury by inhibiting platelet activity via the AKT/NF-κB pathway

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.