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

IF 1.9 4区医学 Q3 HEMATOLOGY

Microcirculation Pub Date : 2022-09-24 DOI:10.1111/micc.12786

Chao Xin, Jinglong Zhang, Ningbo Hao, Jianan Wang, Hui Liu, Hanwen Wei, Yong Wang, Chengzhu Wang, Shuo Wang, Chengrong Zheng, Zheng Zhang, Zhitao Jin

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引用次数: 1

Abstract

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.

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鸢尾素抑制HG/HF培养H/R损伤心肌微血管内皮细胞NLRP3炎性体活化

目的NLRP3炎性体介导心肌缺血再灌注(MI/R)损伤和糖尿病血管内皮功能障碍。然而，NLRP3炎性体在糖尿病心肌梗死/再灌注损伤中的作用尚未得到充分描述。鸢尾素在2型糖尿病患者中具有抗炎和改善内皮功能的重要作用。本研究旨在探讨鸢尾素在糖尿病血管内皮功能障碍中调节NLRP3炎性体激活的作用。方法培养心脏微血管内皮细胞(CMECs)，进行高糖/高脂(HG/HF)缺氧/再氧化(H/R)，鸢尾素孵育或不孵育。然后检测细胞凋亡、活力、迁移、NO分泌和炎性体活化。结果缺氧cmec细胞凋亡增加，细胞活力和迁移能力受损，一氧化氮分泌减少，炎性体活化增强。此外，鸢尾素孵育可降低HG/HF培养的H/R损伤cmes的NLRP3激活并减轻细胞损伤，而NLRP3炎性体激活可消除H/R损伤。同时，NLRP3炎性小体siRNA也能减轻HG/HF条件下cmes的H/R损伤。结论本研究首次证实鸢尾素抑制CMECs NLRP3炎性体激活是糖尿病心肌缺血再灌注损伤的新机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Microcirculation 医学-外周血管病

CiteScore

5.00

自引率

4.20%

发文量

审稿时长

6-12 weeks

期刊介绍： The journal features original contributions that are the result of investigations contributing significant new information relating to the vascular and lymphatic microcirculation addressed at the intact animal, organ, cellular, or molecular level. Papers describe applications of the methods of physiology, biophysics, bioengineering, genetics, cell biology, biochemistry, and molecular biology to problems in microcirculation. Microcirculation also publishes state-of-the-art reviews that address frontier areas or new advances in technology in the fields of microcirculatory disease and function. Specific areas of interest include: Angiogenesis, growth and remodeling; Transport and exchange of gasses and solutes; Rheology and biorheology; Endothelial cell biology and metabolism; Interactions between endothelium, smooth muscle, parenchymal cells, leukocytes and platelets; Regulation of vasomotor tone; and Microvascular structures, imaging and morphometry. Papers also describe innovations in experimental techniques and instrumentation for studying all aspects of microcirculatory structure and function.