Association between angiogenesis soluble factors and disease progression markers in chronic hepatitis C patients

Abstract

Objectives: our objectives were to compare angiogenesis soluble factor (ASF) levels in chronic hepatitis C (CHC) patients and healthy individuals, and to investigate potential associations between ASF levels and both histological and biochemical markers of disease progression.Method: thirty-six patients (69% males) positive for HCV-RNA by PCR analysis were included in the study. All patients underwent liver biopsy before treatment. Serum levels of vascular endothelial growth factor (VEGF), soluble Flt-1 and Flk-1 receptors, placental growth factor (PlGF), angiopoietin-2 (Ang-2) and soluble Tie-2 receptor were determined by ELISA. Fifteen healthy subjects were used as controls.Results: in comparison to healthy individuals, CHC patients showed significantly increased serum levels of proangiogenic factors PlGF (22 ± 5 vs. 18 ± 8 pg/ml; p < 0.05), Ang-2 (1265 ± 385 vs. 833 ± 346 pg/ml; p < 0.005) and sFlt-1 (95 ± 22 vs. 72 ± 14 pg/ml; p < 0.0001). Interestingly, in CHC patients serum levels of VEGF and Tie-2 correlated with grade of inflammation, PlGF correlated with stage of fibrosis, and Flt-1 and Flk-1 correlated with serum transaminase levels (p < 0.05 in all cases).Conclusions: CHC patients showed increased serum levels of ASF, and a significant correlation was shown between serum levels of selected ASFs and grade of inflammation, stage of fibrosis, and transaminase levels.

Peripheral blood monocyte subsets predict antiviral response in chronic hepatitis C

“…Unfortunately, the minimal occurrence of above described monocyte subpopulations in the blood of CHC has hampered the study of their specific functions or the analysis of their respective expression of angiogenic and remodelling factors due to ethical considerations. Nonetheless, this profile of angiogenic factors might reflect the repercussions of adjustments in vessel quiescence, shifting to a more leaky and sprouting vasculature; 44–46 this model is consistent with previous studies of serum in CHC patients who have noted their usefulness in monitoring CHC disease progression 47, 48 . In addition, most of these factors are related to tissue remodelling and their induction is associated with hepatocellular carcinoma onset and progression 47, 49 …”

The ratio of serum placenta growth factor to soluble vascular endothelial growth factor receptor-1 predicts the prognosis of hepatocellular carcinoma

“…These findings indicate that serum PLGF level might reflect the degree of regeneration and inflammation in surrounding non-cancerous liver, in addition to development of pathological angiogenesis in HCC. Actually another group reported that serum PLGF level correlated with grade of fibrosis in chronic hepatitis and liver cirrhosis (26). In this study, high PLGF group had poorer liver function than low PLGF group in patients with HCC.…”

“…Accordingly, VEGFR1 signaling might partly drive activation of sinusoidal endothelial cells, stellate cells and kupffer cells leading to hepatic wound healing, fibrosis and inflammation as well as angiogenesis in HCC tissue. Serum level of sVEGFR1 was reported to be elevated in patient with chronic hepatitis although sVEGFR1 was not detected in normal adults (26). …”

Hypoxia-inducible factor-1α regulates the expression of genes in hypoxic hepatic stellate cells important for collagen deposition and angiogenesis

“…As discussed, angiogenesis is thought to be an essential component of fibrosis. The levels of VEGF, PGF and MIF are increased in patients with chronic liver disease (35–37). Our data suggest that hypoxia may be an important modulator of these mediators in the liver during the development of liver fibrosis.…”