Capillarization of Hepatic Sinusoid by Liver Endothelial Cell-Reactive Autoantibodies in Patients with Cirrhosis and Chronic Hepatitis

Abstract

The special features of liver sinusoidal endothelium (LSE) are crucial for normal liver physiology. Cirrhotic livers, especially in primary biliary cirrhosis (PBC), are characterized by transformation of the LSE into a continuous, vascular type. The transformation is important for disease progression and explains some of the pathological hallmarks of the cirrhotic liver. Here, we investigated the presence of liver sinusoidal endothelial cell (LSEC)-reactive autoantibodies (Abs) in the sera of patients with autoimmune liver diseases, and assessed the ability of these Abs to transform LSE into vascular endothelium. Compared to healthy individuals (9%), significantly higher numbers of patients with PBC (59%; P < 0.001) and autoimmune hepatitis (AIH) (32%; P

Low level arsenic promotes progressive inflammatory angiogenesis and liver blood vessel remodeling in mice

“…The main distinction is that there is no increase in vessel number due to the anatomic constraints of the liver sieve plates. Capillarization of LSEC results in ultrastructural phenotypic conversion to endothelial cells with tight intercellular junctions and loss of fenestrations (Couvelard et al, 1993;Dubuisson et al, 1995;Xu et al, 2003). In multiple human and animal studies, capillarization has been demonstrated to precede alcohol-induced liver disease, portal hypertension, cirrhosis, and chronic hepatitis (DeLeve et al, 2004;Dubuisson et al, 1995;Tsuneyama et al, 2003;Xu et al, 2003).…”

“…Capillarization of LSEC results in ultrastructural phenotypic conversion to endothelial cells with tight intercellular junctions and loss of fenestrations (Couvelard et al, 1993;Dubuisson et al, 1995;Xu et al, 2003). In multiple human and animal studies, capillarization has been demonstrated to precede alcohol-induced liver disease, portal hypertension, cirrhosis, and chronic hepatitis (DeLeve et al, 2004;Dubuisson et al, 1995;Tsuneyama et al, 2003;Xu et al, 2003). Increased SEC membrane PECAM-1 protein expression and deposition of a laminin-1-containing basement membrane are hallmarks of capillarization in injured livers (Couvelard et al, 1993;DeLeve et al, 2004).…”

“…Instead, SEC angiogenesis is a dedifferentiation and maturation process called capillarization with diagnostic hallmarks of SEC defenestration and increased surface expression of PECAM-1 and laminin-1 protein (Braet et al, 2002;DeLeve et al, 2004;Couvelard et al, 1993;Guyot et al, 2006;Tsuneyama et al, 2003). The normally discontinuous SEC become a continuous endothelium with limited transendothelial cell transport due to loss of fenestrae and formation of tight intercellular endothelial junctions (Dubuisson et al, 1995;Braet et al, 2002;Xu et al, 2003;Couvelard et al, 1993). Capillarization precedes vascular remodeling of other liver vessels, such as the hepatic arterioles and the peribiliary vascular plexus causing the shunting of blood flow, vascular channel formation, and eventually liver fibrosis (Couvelard et al, 1993;DeLeve et al, 2004;Li et al, 2005).…”

Hepatic sinusoids in liver injury, inflammation, and fibrosis: new pathophysiological insights

“…Liver injury leads to endothelial dysfunction with loss of fenestrae and deposition of a basement membrane, a process that is known as capillarization [6,15,16]. Besides these morphological changes, changes in paracrine and autocrine function are dramatic, too.…”

Presence of disease specific autoantibodies against liver sinusoidal cells in primary biliary cirrhosis

“…In a similar study, patient sera were incubated with isolated human liver sinusoidal endothelial cells, and 59% of PBC patients had reactive antibodies. Moreover, cells incubated with the F(ab)2 fragments of antibodies from either AIH or PBC patients were transformed into a vascular cell phenotype [34] . Since we used sections of liver tissue rather than isolated cells, our findings are not directly comparable with the results of these studies.…”