Blood angiopoietin-2 predicts liver angiogenesis and fibrosis in hepatitis C patients

BMC Gastroenterology

Masatoshi Imamura¹  Yoshihiko Aoki¹  Masaaki Korenaga¹  Takashi Oide²  Miku Okawara³  Sachiyo Yoshio³  Hironari Kawai³  Yuichi Yoshida³  Shiori Yoshikawa³  Taizo Mori³  Taiji Yamazoe³  Yuriko Tsutsui³  Tatsuya Kanto⁴  Yosuke Osawa⁵ 

[1] Department of Gastroenterology and Hepatology, Kohnodai Hospital, National Center for Global Health and Medicine, 1-7-1 Kohnodai, 272-8516, Ichikawa, Chiba, Japan;Department of Pathology and Laboratory Medicine, Kohnodai Hospital, National Center for Global Health and Medicine, 1-7-1 Kohnodai, 272-8516, Ichikawa, Chiba, Japan;The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohnodai, 272-8516, Ichikawa, Chiba, Japan;The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohnodai, 272-8516, Ichikawa, Chiba, Japan;Department of Gastroenterology and Hepatology, Kohnodai Hospital, National Center for Global Health and Medicine, 1-7-1 Kohnodai, 272-8516, Ichikawa, Chiba, Japan;The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, 1-7-1 Kohnodai, 272-8516, Ichikawa, Chiba, Japan;Department of Gastroenterology, International University of Health and Welfare Hospital, 537-3 Iguchi, 239-2763, Nasushiobara, Tochigi, Japan;Department of Gastroenterology and Hepatology, Kohnodai Hospital, National Center for Global Health and Medicine, 1-7-1 Kohnodai, 272-8516, Ichikawa, Chiba, Japan;

关键词: Angiogenesis;    Angiopoietin-2;    Carbon tetrachloride;    Chronic hepatitis C;    Endothelin-1;    Liver fibrosis;   

DOI  :  10.1186/s12876-021-01633-8

来源: Springer

【 摘 要 】

BackgroundPathological angiogenesis is involved in the development of hepatocellular carcinoma. In patients with chronic hepatitis C (CHC), the level of angiogenic factor angiopoietin (ANGP)-2 is reported to be increased in the blood, correlating with fibrosis. In this study, we aimed to clarify whether blood ANGP-2 is useful as a biomarker for liver angiogenesis and fibrosis in CHC patients and to further reveal the relationship between such pathology in a carbon tetrachloride (CCl4)-treated liver fibrosis mouse model.MethodsPlasma levels of ANGP-2, expression of a liver sinusoidal endothelial cell (LSEC) marker (CD31), collagen deposition (Sirius Red staining) in the liver, clinical fibrosis markers (Mac-2 binding protein glycosylation isomer, virtual touch quantification, and liver stiffness measurement), and liver function (albumin bilirubin score) were examined in CHC patients. To determine the effects of an anti-angiogenic agent on liver fibrosis in vivo, sorafenib was administered to the CCl4-treated mice (BALB/c male).ResultsThe plasma levels of ANGP-2 were increased in CHC patients compared to healthy volunteers and decreased by the eradication of hepatitis C with direct-acting antivirals. In addition, plasma ANGP-2 levels were correlated with CD31 expression, collagen deposition, clinical fibrosis markers, and liver function. Sorafenib inhibited liver angiogenesis and fibrosis in the CCl4-treated mice and was accompanied by decreased ANGP-2 expression in LSECs.ConclusionsANGP-2 may serve as a useful biomarker for liver angiogenesis and fibrosis in CHC patients. In addition, angiogenesis and fibrosis may be closely related.

【 授权许可】

CC BY