Vascular adhesion protein-1 promotes liver inflammation and drives hepatic fibrosis
View abstract on PubMed
Summary
This summary is machine-generated.Vascular adhesion protein-1 (VAP-1) drives liver inflammation and fibrosis in nonalcoholic fatty liver disease (NAFLD). Inhibiting VAP-1's enzyme activity shows therapeutic potential for NAFLD and other chronic liver conditions.
Area Of Science
- Hepatology
- Immunology
- Biochemistry
Background
- Nonalcoholic fatty liver disease (NAFLD) involves liver inflammation and fibrosis.
- Vascular adhesion protein-1 (VAP-1) is an adhesion molecule involved in leukocyte recruitment.
- Soluble VAP-1 (sVAP-1) has insulin-like effects and can induce oxidative stress.
Purpose Of The Study
- To investigate the role of VAP-1 in NAFLD pathogenesis.
- To determine if VAP-1 enzyme activity contributes to liver inflammation and fibrosis.
- To explore VAP-1 as a therapeutic target for chronic liver diseases.
Main Methods
- Assessed hepatic VAP-1 expression and serum sVAP-1 levels in patients.
- Utilized four murine models of hepatic injury.
- Examined the effects of VAP-1 absence, blockade, and catalytic inactivity on liver disease.
- Investigated sVAP-1's effect on leukocyte migration and stromal cell function in vitro.
Main Results
- Hepatic VAP-1 expression and serum sVAP-1 levels were elevated in patients with chronic liver disease and NAFLD.
- VAP-1 deficiency or blockade reduced liver inflammation and fibrosis in mice.
- Catalytically inactive VAP-1 attenuated disease, implicating enzyme activity.
- sVAP-1 promoted leukocyte migration via ROS generation dependent on VAP-1 activity.
Conclusions
- VAP-1 amine oxidase activity is linked to hepatic inflammation and fibrosis in NAFLD.
- Targeting VAP-1 presents a potential therapeutic strategy for NAFLD and other fibrotic liver diseases.