Factor VIII-Related Antigen Detects Phenotypic Change of Sinusoidal to Vascular Endothelium in Hepatic Fibrosis of Elderly Cadavers.

Ki M Mak,Cynthia K Harris,Priya Sehgal

doi:10.1155/2014/839560

Ki M Mak, Cynthia K Harris + Show 1 more

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https://doi.org/10.1155/2014/839560

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Abstract

In advanced stages of hepatic fibrosis, the liver sinusoidal endothelium transforms to vascular endothelium with accompanying expression of factor VIII-related antigen (FVIIIRAg), a phenotypic marker of vascular endothelial cells. Liver fibrosis has been shown to be associated with aging and was found to be prevalent in elderly cadavers. Using immunohistochemistry, we studied FVIIIRAg expression in the livers of elderly cadavers with progressive stages of fibrosis. The vascular endothelium of portal tracts and central veins was stained for FVIIIRAg, providing an internal positive control. The incidence of FVIIIRAg expression was low in the sinusoids of livers that showed minimal fibrosis or perisinusoidal fibrosis but was increased in livers with advanced fibrosis (i.e., septa formation, bridging fibrosis, and cirrhosis). FVIIIRAg positive sinusoidal endothelial cells were distributed in loose aggregates in the periportal, periseptal, and midlobular parenchyma and were found less frequently in the centrilobular area. FVIIIRAg immune deposits appeared patchy and discontinuous along the sinusoidal lining, likely representing focalized transformation of sinusoidal to vascular endothelium. There was a discrete localization of FVIIIRAg immunoreactivity in the foci of severe parenchymal fibrosis. Conclusion. FVIIIRAg is a reliable marker for detecting the transformation of sinusoidal to vascular endothelium in advanced liver fibrosis in elderly cadavers.

Highlights

The liver parenchyma is extensively supplied by sinusoids that are lined by endothelial cells, which contain fenestrae but lack a continuous basal lamina when viewed by electron microscopy [1, 2]
To test whether FVIIIRAg can be used as a phenotypic marker for the vascular endothelium in the cadaveric liver, we examined the antigen immunoreactivity in the endothelium of portal tracts and central veins
These findings demonstrate that FVIIIRAg expression represents a reliable phenotypic marker of the vascular endothelium of the systemic vasculature

Summary

Introduction

The liver parenchyma is extensively supplied by sinusoids that are lined by endothelial cells, which contain fenestrae but lack a continuous basal lamina when viewed by electron microscopy [1, 2]. In chronic liver diseases with severe fibrotic changes, the fenestrated endothelial cells undergo striking morphological changes to nonfenestrated endothelial cells accompanied by the appearance of a basal lamina, forming vascular type endothelium or continuous capillaries as seen in the systemic vasculature. This transformation represents a significant pathology known as the capillarization of hepatic sinusoids [7], which can be observed in alcoholic liver disease, primary biliary cirrhosis, and autoimmune hepatitis [8,9,10], as well as experimental hepatic cirrhosis in rats [4, 11, 12]. The development of capillarized sinusoids will cause a perturbation in hepatic microcirculation and compromise the exchange of materials across the endothelium and the space of Disse between the sinusoidal blood and parenchymal cells [4]

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