Irisin inhibits NLRP3 inflammasome activation in HG/HF incubated cardiac microvascular endothelial cells with H/R injury

• Published in: Microcirculation (New York, N.Y. 1994) N.Y. 1994), 2022-11, Vol.29 (8), p.e12786-n/a
• Main Authors: Xin, Chao, Zhang, Jinglong, Hao, Ningbo, Wang, Jianan, Liu, Hui, Wei, Hanwen, Wang, Yong, Wang, Chengzhu, Wang, Shuo, Zheng, Chengrong, Zhang, Zheng, Jin, Zhitao
• Format: Article
• Language: English
• Subjects: Apoptosis; CMECs; Diabetes; Diabetes Mellitus, Type 2; Endothelial Cells; Fibronectins - pharmacology; Humans; Inflammasomes - pharmacology; irisin; Ischemia; myocardial ischemia/reperfusion; Myocardial Reperfusion Injury; NLR Family, Pyrin Domain-Containing 3 Protein - genetics; NLRP3 inflammasome; Reperfusion Injury
• ISSN: 1073-9688; 1549-8719
• DOI: 10.1111/micc.12786

Purpose NLRP3 inflammasome mediates myocardial ischemia/reperfusion (MI/R) injury and diabetic vascular endothelia dysfunction. However, the role of NLRP3 inflammasome in MI/R injury with diabetes has not been fully described. Irisin plays an important role in anti‐inflammation and improves endothelial function in type 2 diabetes. The current study aimed to investigate the effect of irisin on regulating NLRP3 inflammasome activation in diabetic vascular endothelia dysfunction. Methods Cardiac microvascular endothelial cells (CMECs) were cultured and subjected to high glucose/high fat (HG/HF) receiving hypoxia/reoxygenation (H/R) with irisin incubation or not. Then, apoptosis, viability, migration, NO secretion, and inflammasome activation were examined. Results The hypoxic CMECs exhibited increased apoptosis, impaired viability, and migration, even decreased NO secretion and enhanced inflammasome activation. Moreover, irisin incubation decreased NLRP3 activation and attenuated cell injury in HG/HF cultured CMECs subjected to H/R injury, which was abolished by NLRP3 inflammasome activation. Meanwhile, NLRP3 inflammasome siRNA also attenuated H/R injury in CMECs under HG/HF condition. Conclusion The current study demonstrated for the first time that irisin inhibits NLRP3 inflammasome activation in CMECs as a novel mechanism in myocardial ischemia/reperfusion injury in diabetes.