Nuanxinkang (NXK) ameliorates Piezo1-mediated pyroptosis post-myocardial infarction

Abstract

Aim of the studyThis study aims to identify the effects of Nuanxinkang (NXK) on inflammation and pyroptosis post-MI and understand the underlying mechanisms. Materials and methodsLeft Anterior Descending (LAD) coronary artery ligation was used to induce MI in mice. NXK or Captopril were orally administered 3 days after surgery for 4 weeks. Cardiac function, as well as infarct size, was detected by echocardiography, 2,3,5-triphenyl-tetrazolium chloride (TTC) staining and Hematoxylin and Eosin (H&E) staining. Inflammatory mediators were measured by flow cytometry, real-time polymerase chain reaction (RT-PCR) and immunofluorescence (IF). Pyroptosis-related protein expressions were determined through Western blot (WB). Intracellular Ca2+ measurements were conducted in bone marrow derived macrophages (BMDM) to detect calcium influx. Molecular docking (MD) was applied to define the candidate ingredients in NXK that regulate Piezo1. ResultsNXK increased the ratio of heart or lung and body weight in mice post-MI. TTC and H&E staining infarct size and myocardial damage. The results obtained through echocardiography suggest that NXK remarkably enhanced heart function. Immunofluorescence of F4/80 and flow cytometry results demonstrated that NXK suppressed inflammatory infiltration. Molecular docking showed that Piezo1 had correlation with NXK. Intracellular Ca2+ measurements suggest that NXK inhibit Yoda1-evoked Piezo1 activation. Furthermore, NXK treatment significantly suppressed Piezo1-mediated pyroptosis in vivo and in vitro. ConclusionsThe present study indicates that NXK may prevent ventricular remodeling post-MI through regulation of the Piezo1-mediated pyroptosis. Furthermore, the study provides a potential strategy for attenuating NLRP3-inflmmasome activation in the context of ventricular remodeling post-MI using NXK.