Free fatty acids stabilize integrin ß1via S-nitrosylation to promote monocyte-endothelial adhesion.
J Biol Chem
; 299(1): 102765, 2023 01.
Article
em En
| MEDLINE
| ID: mdl-36470423
ABSTRACT
Hyperlipidemia characterized by high blood levels of free fatty acids (FFAs) is important for the progression of inflammatory cardiovascular diseases. Integrin ß1 is a transmembrane receptor that drives various cellular functions, including differentiation, migration, and phagocytosis. However, the underlying mechanisms modifying integrin ß1 protein and activity in mediating monocyte/macrophage adhesion to endothelium remain poorly understood. In this study, we demonstrated that integrin ß1 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 ß1 expression, we treated the macrophages with a combination of oleic acid and palmitic acid (21) and found that FFA activated inducible nitric oxide synthase/nitric oxide and increased the integrin ß1 protein level without altering the mRNA level. FFA promoted integrin ß1 S-nitrosylation via inducible nitric oxide synthase/nitric oxide and prevented its degradation by decreasing binding to E3 ubiquitin ligase c-Cbl. Furthermore, we found that increased integrin α4ß1 heterodimerization resulted in monocyte/macrophage adhesion to endothelium. In conclusion, these results provided novel evidence that FFA-stimulated N--O stabilizes integrin ß1via S-nitrosylation, favoring integrin α4ß1 ligation to promote vascular inflammation.
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Base de dados:
MEDLINE
Assunto principal:
Monócitos
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Células Endoteliais
/
Ácidos Graxos não Esterificados
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article