Department of Internal Medicine, Kitasato Medical Center Hospital, Kitasato University Department of Rehabilitation, Nihon Institute of Medical Science, Saitama Organized Center of Clinical Medicine, and Department of Internal Medicine, Sanno Medical Center, International University of Health and Welfare Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Hepatol Res. 2012 May;42(5):508-14. doi: 10.1111/j.1872-034X.2011.00945.x.
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.
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.
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.
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.
apelin (APLN) 是血管紧张素样受体 1 (APJ) 的内源性配体，是胚胎和肿瘤血管生成所必需的肽。关于 APLN 表达的定位和变化知之甚少，包括在人类肝硬化的窦状隙中，这可能有助于门脉高压的形成。本研究旨在阐明 APLN 在肝硬化进展过程中在人肝中的定位和表达变化。
研究了 12 例正常肝标本、8 例 Child-Pugh 分级 A 肝硬化标本和 10 例 Child-Pugh 分级 C 肝硬化标本。通过免疫组化、western blot、免疫电镜和激光捕获显微切割（LCM）后聚合酶链反应（PCR）检测窦状隙中 APLN 蛋白和基因表达。
在正常肝组织中，APLN 主要定位于门脉区动脉内皮细胞和肝动脉。在肝硬化肝组织中，在与毛细血管化窦状隙相对应的门周毛细血管内皮细胞中观察到异常的 APLN 表达，并在纤维间隔中的增生性动脉毛细血管中观察到。western blot 显示肝硬化肝组织中 APLN 蛋白表达显著增加（P < 0.01 Child-Pugh A 和 C 与对照相比，P < 0.01 Child-Pugh A 与 C 相比）。通过 LCM-PCR 证实了窦状隙中 APLN mRNA 的表达。
在人类中，与正常肝相比，肝硬化肝中 APLN 蛋白和基因过度表达，并且随着肝硬化的进展而增加。特别是在终末期肝硬化中，APLN 在与窦状隙直接相连的增生性动脉毛细血管中强烈表达，提示 APLN 在肝硬化中动脉毛细血管增生中的作用。
