Free fatty acids stabilize integrin β 1 via S-nitrosylation to promote monocyte-endothelial adhesion.

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 α4 β1 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 α4 β1 ligation to promote vascular inflammation.