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

作者：Yao, Qinyu; Cui, Qi; Liu, Jia; Xie, Xinya; Jiang, Tingting; Wang, Haodong; Zhao, Ziwei; Zhao, Wenfei; Du, Xiong; Lai, Baochang; Xiao, Lei; Wang, Nanping^*

来源：Journal of Biological Chemistry, 2023, 299(1): 102765.

DOI：10.1016/j.jbc.2022.102765

• DEGRADATION
• STRESS
• INFLAMMATION
• PHENOTYPE
• MIGRATION
• BINDING

Hyperlipidemia characterized by high blood levels of free fatty acids (FFAs) is important for the progression of inflam-matory cardiovascular diseases. Integrin beta 1 is a trans -membrane receptor that drives various cellular functions, including differentiation, migration, and phagocytosis. How-ever, the underlying mechanisms modifying integrin beta 1 pro-tein and activity in mediating monocyte/macrophage adhesion to endothelium remain poorly understood. In this study, we demonstrated that integrin beta 1 protein underwent S-nitrosylation in response to nitrosative stress in macro-phages. To examine the effect of elevated levels of FFA on the modulation of integrin beta 1 expression, we treated the macro-phages with a combination of oleic acid and palmitic acid (2:1) and found that FFA activated inducible nitric oxide synthase/ nitric oxide and increased the integrin beta 1 protein level without altering the mRNA level. FFA promoted integrin beta 1 S-nitro-sylation via inducible nitric oxide synthase/nitric oxide and prevented its degradation by decreasing binding to E3 ubiq-uitin ligase c-Cbl. Furthermore, we found that increased integrin alpha 4 beta 1 heterodimerization resulted in monocyte/ macrophage adhesion to endothelium. In conclusion, these results provided novel evidence that FFA-stimulated N-O stabilizes integrin beta 1 via S-nitrosylation, favoring integrin alpha 4 beta 1 ligation to promote vascular inflammation.

• 单位
  西安交通大学; 河北医科大学