Enhanced expressions of apelin on proliferative hepatic arterial capillaries in human cirrhotic liver.

ABSTRACT

AIM: Apelin (APLN), the endogenous ligand of angiotensin-like receptor 1 (APJ), is a peptide necessary for embryonic and tumor angiogenesis. Little is known about the localization and changes of APLN expression including the sinusoids in human cirrhotic liver, which might contribute to portal hypertension. This study was designed to elucidate the localization and change of APLN expression in human liver during the progression of cirrhosis. METHODS: Twelve normal liver specimens, eight specimens of Child-Pugh grade A cirrhosis, and 10 specimens of Child-Pugh grade C cirrhosis were studied. APLN protein and gene expression was examined by immunohistochemistry, western blotting, immunoelectronic microscopy, and laser captured microdissection (LCM) followed by polymerase chain reaction (PCR) in sinusoid. RESULTS: In control liver tissue, APLN was localized mainly on arterial endothelial cells and hepatic arterioles in the portal tract. In cirrhotic liver tissue, aberrant APLN expression was observed in periportal capillary endothelial cells corresponding to capillarized sinusoids, and in proliferated arterial capillaries in the fibrotic septa. Significant overexpression of APLN at protein level in cirrhotic liver was demonstrated by western blotting (P < 0.01 Child-Pugh A and C versus control, P < 0.01 Child-Pugh A versus C). APLN mRNA expression in the sinusoid was confirmed by LCM-PCR. CONCLUSION: In humans, APLN protein and gene were overexpressed in cirrhotic liver compared with normal liver, and the magnitude increased as cirrhosis progressed. Especially in end-stage cirrhosis, APLN was strongly expressed in proliferated arterial capillaries directly connected with the sinusoids, suggesting a role of APLN in the proliferation of arterial capillaries in cirrhosis.