Uric acid aggravates myocardial ischemia-reperfusion injury via ROS/NLRP3 pyroptosis pathway.

The NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome activation-mediated pyroptosis pathway has been linked to myocardial ischemia-reperfusion (MI/R) injury. This study explored whether uric acid (UA) aggravates MI/R injury through NLRP3 inflammasome-mediated pyroptosis. In vivo, a mouse MI/R model was established by ligating the left coronary artery, and a mouse hyperuricemia model was created by intraperitoneal injection of potassium oxonate (PO). Then, the myocardial infarction (MI) size; terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) immunofluorescence; and serum levels of lactate dehydrogenase (LDH), creatine kinase isoenzyme (CK-MB), and UA, as well as the expression level of pyroptosis-related protein and caspase-3 in heart tissues, were measured. Separately, primary mouse cardiomyocytes were cultured in vitro to create a hypoxia/reoxygenation (H/R) model. We then compared cardiomyocytes viability, TUNEL immunofluorescence, and the levels of LDH, reactive oxygen species (ROS), and pyroptosis-related protein and caspase-3 in cardiomyocytes. In vivo, the MI area, levels of CK-MB and LDH, rate of cell death, and pyroptosis-related protein and the expression of caspase-3 were significantly higher in the MI/R group than in the sham group, and high UA levels worsened these changes. In vitro, cardiomyocytes viability was significantly downregulated, and the levels of ROS, LDH, pyroptosis-related protein, caspase-3, and the rate of cardiomyocyte death were significantly higher in the H/R + UA group compared with the HR group. Administration of an NLRP3 inflammasome inhibitor and ROS scavenger reversed these effects. UA aggravates MI/R-induced activation of the NLRP3 inflammatory cascade and pyroptosis by promoting ROS generation, while inflammasome inhibitors and ROS scavengers partly reverse the injury.

Shen S ，He F ，Cheng C ，Xu B ，Sheng J ... -  《-》

Lipopolysaccharide (LPS) Aggravates High Glucose- and Hypoxia/Reoxygenation-Induced Injury through Activating ROS-Dependent NLRP3 Inflammasome-Mediated Pyroptosis in H9C2 Cardiomyocytes.

Qiu Z ，He Y ，Ming H ，Lei S ，Leng Y ，Xia ZY ... -  《-》

NLRP3 Inflammasome Activation-Mediated Pyroptosis Aggravates Myocardial Ischemia/Reperfusion Injury in Diabetic Rats.

Qiu Z ，Lei S ，Zhao B ，Wu Y ，Su W ，Liu M ，Meng Q ，Zhou B ，Leng Y ，Xia ZY ... -  《-》

Metformin protects against myocardial ischemia-reperfusion injury and cell pyroptosis via AMPK/NLRP3 inflammasome pathway.

Zhang J ，Huang L ，Shi X ，Yang L ，Hua F ，Ma J ，Zhu W ，Liu X ，Xuan R ，Shen Y ，Liu J ，Lai X ，Yu P ... -  《Aging-US》

High-dose remifentanil exacerbates myocardial ischemia-reperfusion injury through activation of calcium-sensing receptor-mediated pyroptosis.

Zhu Y ，Chi J ，Cai S ，Liu S ，Yuan J ，Xu H ，Zhou H ... -  《International Journal of Medical Sciences》