SerpinA3 Promotes Myocardial Infarction in Rat and Cell-based Models

This study aimed to examine the role and molecular mechanism of the nuclear factor kappa B (NF kappa B)/serine protease inhibitor A3 (SerpinA3) interaction in myocardial ischemia-reperfusion (IR) injury. First, a rat model for myocardial ischemia-reperfusion injury was established, using 2,3,5-triphenyltetrazolium chloride to measure the size of the myocardial infarction. Pathological variations in myocardial tissue were detected using hematoxylin-eosin staining. Flow cytometry and terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining were used to measure cell death in the rat model. The SerpinA3 mRNA and protein expressions in the myocardium of IR-model rats were remarkably higher than those in the control group. Furthermore, the oxidative, inflammatory, and apoptotic activities of the myocardial tissue of SerpinA3-knockdown (KD) rats were significantly improved compared to those in the WT group. SerpinA3-KD also contributed to the recovery of cardiac function in IR-model rats. Additionally, silencing of SerpinA3 inhibited p65 phosphorylation in myocardial tissues and reduced H2O2-induced inflammation, oxidative stress, and apoptosis in myocardial cells. The expression of SerpinA3 increased in myocardial tissue after IR stimulation. Knockdown of SerpinA3 can deactivate NF-kappa B and reduce inflammation, oxidative stress, and apoptosis in vivo and in vitro, thereby lessening myocardial injury caused by IR. In conclusion, SerpinA3 promotes myocardial infarction in rat and cell-based models by activating NF-kappa B. However, the mechanism by which increased Serpina3 expression causes downstream NF-kappa B activation to mediate the proposed, pathological effects in myocardial IR injury remain untested and worthy of future investigations.

Automated summary

This study investigated the role and molecular mechanism of nuclear factor kappa B (NFκB) and serine protease inhibitor A3 (SerpinA3) interaction in myocardial ischemia-reperfusion (IR) injury. The results demonstrated that increased expression of SerpinA3 activates NFκB and contributes to myocardial infarction. Silencing of SerpinA3 reduces inflammation, oxidative stress, and apoptosis, thus protecting the myocardium.