Serum levels of vascular endothelial growth factor in non-alcoholic fatty liver disease

Abstract

BackgroundThis study aimed to assess the significance of serum levels of vascular endothelial growth factor (VEGF) in non-alcoholic fatty liver disease (NAFLD).MethodsSixty-seven consecutive NAFLD patients and 47 healthy controls who visited our liver clinics between May 2008 and December 2010 were included. The NAFLD diagnosis required elevated alanine aminotransferase and/or gamma-glutamyl transpeptidase levels, evidence of hepatic steatosis on ultrasound and/or liver histology, and exclusion of other causes of liver injury. Serum VEGF levels were determined by an enzyme immunoassay. Liver biopsy was obtained in 34 NAFLD patients. Histological lesions were scored by a liver histopathologist.ResultsSerum VEGF levels tended to be lower in matched NAFLD patients than in healthy controls (296±146 vs. 365±186 pg/mL, P=0.092); levels in patients with non-alcoholic steatohepatitis (NASH) also tended to be lower than in those with simple fatty liver (FL) (279±149 vs. 359±190 pg/mL, P=0.095); while VEGF levels were significantly lower in NASH patients than in healthy controls (279±149 vs. 365±186 pg/mL, P=0.041). VEGF levels offered poor predictability for the differentiation between NAFLD patients and controls or between NASH and FL patients. However, patients with high VEGF levels (≥300 pg/mL) were significantly more likely to have FL, either in the total NAFLD population (67% vs. 35%, P=0.019) or in the 34 NAFLD patients with liver biopsy (57% vs. 15%, P=0.023), while those with high VEGF levels also had a significantly lower mean fibrosis score (0.7±0.9 vs. 1.6±1.0, P=0.017).ConclusionOur data suggest that serum VEGF levels are equally high in healthy controls and in patients with simple fatty liver, but tend to decrease when NASH develops.

Hepatic Stellate Cell Activation and Inactivation in NASH-Fibrosis—Roles as Putative Treatment Targets?

“…The pharmacological stimulation of nitric oxide production in rats with thioacetamide-induced liver cirrhosis restored the differentiated LSEC phenotype, which subsequently led to the apoptosis and inactivation of aHSCs [ 133 ]. While studies have shown lower vascular endothelial growth factor A levels in NASH patients compared to healthy controls or to patients with bland steatosis, hepatic angiogenesis driven by vascular endothelial growth factor A is thought to aid fibrogenesis; therefore, possible interventions targeting LSEC-mediated HSC inactivation should concentrate on downstream effectors [ 134 , 135 , 136 ].…”

VEGFA mRNA-LNP promotes biliary epithelial cell-to-hepatocyte conversion in acute and chronic liver diseases and reverses steatosis and fibrosis

“…Although, we cannot conclude about the function of non-glycosylated isoform of KDR in hepatocytes, it serves here as a surrogate lineage tracing mapping the hepatocytic cell fate of KDR-expressing BECs. In line with the notion of VEGFA as a therapeutic target for advanced liver diseases, a recent study has shown a significant correlation between high levels of serum VEGF and lower fibrosis score in a NAFLD cohort (Papageorgiou et al, 2017), suggesting a protective effect of VEGFA against progression of the disease. Yet, the study indicates that levels of serum VEGF tend to decrease when NASH develops, offering a potential therapeutic intervention for VEGFA mRNA-LNP to mitigate the liver disease.…”

Prognostication of endothelial dysfunction in patients with non-alcoholic fatty liver diseases

“…На сьогоднішній день сформульована концепція ЕД як центральної ланки патогенезу багатьох хронічних хвороб. Основну роль у розвитку ЕД відіграють оксидативний стрес, синтез потужних вазоконстрикторів, які пригнічують утворення оксиду азоту [7].…”