1. Academic Validation
  2. Free fatty acids stabilize integrin β1 via S-nitrosylation to promote monocyte-endothelial adhesion

Free fatty acids stabilize integrin β1 via S-nitrosylation to promote monocyte-endothelial adhesion

  • J Biol Chem. 2022 Dec 2;102765. doi: 10.1016/j.jbc.2022.102765.
Qinyu Yao 1 Qi Cui 2 Jia Liu 1 Xinya Xie 3 Tingting Jiang 2 Haodong Wang 4 Ziwei Zhao 2 Wenfei Zhao 3 Xiong Du 3 Baochang Lai 1 Lei Xiao 1 Nanping Wang 5
Affiliations

Affiliations

  • 1 Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, China; Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education of China, Xi'an, China.
  • 2 Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, 116044, China.
  • 3 Cardiovascular Research Center, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, China.
  • 4 East China Normal University Health Science Center, Shanghai, 200241, China.
  • 5 East China Normal University Health Science Center, Shanghai, 200241, China. Electronic address: npwang@hsc.ecnu.edu.cn.
Abstract

Hyperlipidemia characterized by high blood levels of free fatty acids (FFA) is important for the progression of inflammatory cardiovascular diseases. Integrin β1 is a transmembrane receptor that drives various cellular functions, including differentiation, migration, and phagocytosis. However, the underlying mechanisms modifying Integrin β1 protein and activity in mediating monocyte/macrophage adhesion to endothelium remain poorly understood. In this study, we demonstrated that Integrin β1 protein underwent S-nitrosylation in response to nitrosative stress in macrophages. To examine the effect of elevated levels of FFA on the modulation of Integrin β1 expression, we treated the macrophages with a combination of oleic acid and palmitic acid (2:1) and found that FFA activated inducible nitric oxide synthase (iNOS)/nitric oxide (NO) and increased the Integrin β1 protein level without altering the mRNA level. FFA promoted Integrin β1 S-nitrosylation via iNOS/NO and prevented its degradation by decreasing binding to E3 ubiquitin Ligase c-Cbl. Furthermore, we found that increased Integrin α4β1 heterodimerization resulted in monocyte/macrophage adhesion to endothelium. In conclusion, these results provided novel evidence that FFA-stimulated NO stabilizes Integrin β1 via S-nitrosylation, favoring Integrin α4β1 ligation to promote vascular inflammation.

Keywords

Nitric oxide; S-nitrosylation; endothelial cell; integrin; macrophage.

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