NLRP3 inflammasome mediate palmitate-induced endothelial dysfunction

LIFE SCIENCES

卷:239

Article

Xing, Jun-hui¹  Li, Rui²  Gao, Yue-qiao³  Wang, Meng-yu¹  Liu, Yu-zhou¹  Hong, Jin¹  Dong, Jian-zeng¹  Gu, He-ping¹  Li, Ling¹ 

[1] Zhengzhou Univ, Affiliated Hosp 1, Dept Cardiol, 1 Jianshe East Rd, Zhengzhou 450052, Henan, Peoples R China

[2] China Japan Friendship Hosp, Minist Hlth, Dept Hlth Care, Beijing, Peoples R China

[3] Zhengzhou Univ, Affiliated Hosp 1, Dept Endocrinol, Zhengzhou, Henan, Peoples R China

关键词: NLRP3 inflammasome;    Endothelial dysfunction;    Inflammation;    Insulin resistance;   

DOI  :  10.1016/j.lfs.2019.116882

来源: Elsevier

【 摘 要 】

Aims: Free fatty acids (FFA) is a key contributor to insulin resistance and endothelial dysfunction. However, the precise mechanism underlying the role of FFA remains elusive. This study aimed to investigate the role of NLRP3 (NOD-like receptor pyrin domain containing-3) inflammasome in FFA induced endothelial dysfunction. Main methods: HUVECs were transfected with NLRP3 siRNA and then stimulated with LPS and palmitate. C57 BL/6 J mice transfected with NLRP3 Lenti-Virus were fed with a high-fat diet (HFD). The levels of NLRP3 inflammasome, AMPK alpha (AMP-activated protein kinase), endothelial nitric oxide synthase (eNOS) and the activity of the insulin signal pathway, in endothelial cells were determined via Western blotting. Endothelial function was determined by measuring the level of endothelium-dependent vasodilatation. Key findings: FFA could activate NLRP3 inflammasome and induce IL-1 beta release both in vitro. and in vivo. Using siRNA and Lenti-Virus to inhibit NLRP3 abolished palmitate-induced IL-1 beta release and restored impaired phosphorylation of IRS-1 (Tyr), Akt (Ser473) and eNOS (Ser1177) and ACh-mediated endothelium-dependent vasorelaxation induced by palmitate. AMPK alpha activator AICAR(5-aminoimidazole-4-carbox-amide-1-beta-d-ribofuranoside) inhibited NLRP3 inflammasome activation and decreased IL-1 beta release and restored impaired insulin signal pathway induced by palmitate. Significance: NLRP3 inflammasome activation via AMPK alpha inactivation mediated palmitate-induced endothelial dysfunction through involves IL-1 beta-induced insulin signal pathway.

【 授权许可】

Free