Evaluation of inflammatory and angiogenic factors in patients with non-alcoholic fatty liver disease

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2012-08, Vol.59 (2), p.442-449
• Main Authors: Coulon, Stephanie, Francque, Sven, Colle, Isabelle, Verrijken, An, Blomme, Bram, Heindryckx, Femke, De Munter, Steffi, Prawitt, Janne, Caron, Sandrine, Staels, Bart, Van Vlierberghe, Hans, Van Gaal, Luc, Geerts, Anja
• Format: Article
• Language: English
• Subjects: adipose tissue; Adult; Americans; angiogenesis; Angiogenesis Inducing Agents - blood; Angiogenesis Inducing Agents - metabolism; Biopsy; blood serum; Case-Control Studies; fatty liver; Fatty Liver - blood; Fatty Liver - genetics; Fatty Liver - pathology; Female; gene expression; Gene Expression Regulation; Health; Humans; Inflammation - blood; Inflammation - genetics; Inflammation - pathology; Interleukin 6; Interleukin-6 - blood; Linear Models; liver; Liver - metabolism; Liver - pathology; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; pathophysiology; patients; Tumor necrosis factor alpha; Tumor Necrosis Factor-alpha - blood; Vascular endothelial growth factor; vascular endothelial growth factor A; Vascular Endothelial Growth Factor A - blood; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - metabolism; Vascular endothelial growth factor receptor; Vascular Endothelial Growth Factor Receptor-1 - blood; Vascular Endothelial Growth Factor Receptor-1 - genetics; Vascular Endothelial Growth Factor Receptor-1 - metabolism; Vascular Endothelial Growth Factor Receptor-2 - blood; Vascular Endothelial Growth Factor Receptor-2 - genetics; Vascular Endothelial Growth Factor Receptor-2 - metabolism; vascular endothelial growth factor receptors; Young Adult
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2012.05.001

► Serum concentration of inflammatory and angiogenic factors in NAFLD patients. ► Gene expression of inflammatory and angiogenic factors in liver of NAFLD patients. ► TNFα and IL6 levels are increased in serum of NAFLD patients compared to controls. ► VEGF and sVEGFR1 levels are increased in serum of NAFLD patients compared to controls. ► TNF gene expression is higher in liver of NASH patients compared to steatosis patients. The liver is a major target of injury in obese patients. Non-alcoholic fatty liver disease (NAFLD) is present in 60–90% of obese Americans and can range from simple steatosis to the more severe non-alcoholic steatohepatitis (NASH). The onset of a chronic inflammatory reaction marks the progression from simple steatosis to NASH and the expansion of adipose tissue is strongly associated with angiogenesis. Therefore, we determined the serum concentration of inflammatory [tumor necrosis factor alpha (TNFα) and interleukin 6 (IL6)] and angiogenic [vascular endothelial growth factor A (VEGF)] cytokines and soluble VEGF receptors 1 and 2 (sVEGFR1, sVEGFR2) in the serum of an obese population with simple steatosis and NASH compared to healthy controls. Moreover, we determined the TNFα, IL6, VEGF, VEGFR1 and VEGFR2 gene expression in the liver of these simple steatosis and NASH patients. The population consisted of 30 obese patients, which were diagnosed with simple steatosis and 32 patients with NASH and compared to 30 age-and-sex matched healthy controls. Mean serum TNFα levels were elevated in the serum of simple steatosis and NASH patients compared to healthy controls, reaching significance in NASH patients. IL6 was significantly increased in simple steatosis and NASH patients compared to the healthy controls. VEGF levels were significantly elevated in patients with simple steatosis and borderline significantly elevated in NASH patients compared to the serum levels of healthy control subjects. The concentration of sVEGFR1 was significantly increased in serum of simple steatosis and NASH patients compared to controls. sVEGFR2 concentration was not significantly different in the three groups. TNFα mRNA expression was higher in NASH patients compared to simple steatosis patients. Hepatic gene expression of VEGF, VEGFR1 and VEGFR2 were slightly decreased in NASH patients compared to simple steatosis patients. These data indicate the involvement of inflammatory (TNFα and IL6), angiogenic (VEGF) cytokines and sVEGFR1 in the pathophysiology of NAF