title: Curcumin ameliorates intrahepatic angiogenesis and capillarization of the sinusoids in carbon tetrachloride-induced rat liver fibrosis.
abstract: Neoangiogenesis and the development of an abnormal angio-architecture in the liver are strongly linked with progressive fibrogenesis. This study aimed to evaluate the ability of curcumin to protect liver fibrosis-associated angiogenesis and capillarization of the sinusoids in experimental rats. Liver fibrosis was induced by intraperitoneal injection of carbon tetrachloride (CCl₄) with or without curcumin for 6 weeks. The results suggest that curcumin treatment markedly attenuated CCl₄-induced liver fibrosis, as assessed by histology and hydroxyproline content, and inhibited hepatic stellate cell activation. Curcumin ameliorated hepatic angiogenesis, as assessed by measuring microvessel density using Von Willebrand factor staining and by examining the expression of the endothelial cell markers CD31 and vascular endothelial growth factor receptor (VEGFR)-2 in the livers. Pathologic remodeling of liver sinusoidal capillarization, as assessed by electron-microscopic analysis of Disse's space and by evaluation of the levels of basement membrane protein expression, was also attenuated by curcumin administration. The intrahepatic gene or protein expression of hypoxia-inducible factor-1α, VEGFR-1, placental growth factor, and cyclooxygenase-2 decreased with treatment with curcumin in fibrotic rats. In conclusion, curcumin ameliorates hepatic angiogenesis and sinusoidal capillarization in CCl₄-induced rat liver fibrosis through suppressing multiple proangiogenic factors.
authors.affiliation: Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai 200032, People's Republic of China.
authors.forename: Qunyan
authors.initials: Q
authors.lastname: Yao
authors.forename: Yizheng
authors.initials: Y
authors.lastname: Lin
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.forename: Xizhong
authors.initials: X
authors.lastname: Shen
authors.forename: Jiyao
authors.initials: J
authors.lastname: Wang
authors.forename: Chuantao
authors.initials: C
authors.lastname: Tu
mesh_terms: D020533:Angiogenesis Inhibitors; D000818:Animals; D015153:Blotting, Western; D002196:Capillaries / Q000187:drug effects / Q000473:pathology*; D002252:Carbon Tetrachloride Poisoning / Q000473:pathology* / Q000517:prevention & control*; D003474:Curcumin / Q000494:pharmacology*; D006504:Hepatic Veno-Occlusive Disease / Q000473:pathology* / Q000517:prevention & control*; D006909:Hydroxyproline / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008103:Liver Cirrhosis / Q000473:pathology* / Q000517:prevention & control*; D008297:Male; D046529:Microscopy, Electron, Transmission; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D020533:Angiogenesis Inhibitors; D003474:Curcumin; D006909:Hydroxyproline
keywords: Angiogenesis; CCl(4); COX-2; Cirrhosis; Curcumin; ECM; HIF-1α; HMGB1; HSC; Liver fibrosis; PlGF; SECs; Sinusoidal capillarization; TEM; TGF-β1; TNF-α; VEGF; VEGFR; alpha-smooth muscle actin; carbon tetrachloride; cyclooxygenase-2; extracellular matrix; hepatic stellate cells; high-mobility group box 1; hypoxia-inducible factor-1α; placental growth factor; sinusoidal endothelial cells; transforming growth factor-beta1; transmission electron microscopy; tumor necrosis factor; vWF; vascular endothelial growth factor; vascular endothelial growth factor receptor; von Willebrand factor; α-SMA