Liver sinusoidal endothelial cells (LSECs) modifications in patients with chronic hepatitis C

Abstract

The sinusoidal endothelial cells present in the liver (LSECs) are tipically characterized by the presence of pores (fenestrae). During some pathological conditions LSECs undergo “capillarization”, a process characterized by loss of fenestrations and acquisition of a vascular phenotype. In chronic liver disease capillarization has been reported to precede the development of fibrosis. LSECs modification in the setting of HCV infection is currently poorly investigated. Considering that HCV accounts for important changes in hepatocytes and in view of the intimate connection between hepatocytes and LSECs, here we set out to study in great detail the LSECs modifications in individuals with HCV-dependent chronic hepatitis. Electron microscopy analysis, and evaluation of CD32, CD31 and caveolin-1 expression showed that in HCV infection LSECs display major morphological changes but maintain their phenotypical identity. Capillarization was observed only in cases at initial stages of fibrosis. Our findings showed that the severity of LSECs modifications appears to be correlated with hepatocytes damage and fibrosis stage providing novel insight in the pathogenesis of HCV-chronic hepatitis.

MRI contrast enhancement of liver pre-neoplasia using iron–tannic nanoparticles

“…Similarly, CD34 staining, endothelial cell markers clearly show the CD34positive capillaries and sinusoids of liver tissue in the control rats, but not for DEN induced rats, implying that there are abnormalities of liver sinusoidal endothelial cells (LSECs). 23 Because hepatic sinusoid acts as a selective barrier between the blood and liver parenchyma, alteration of sinusoidal functions and morphologies might lead to leakage of hepatic capillaries and sinusoids, thereby causing Fe-TA NPs to penetrate liver parenchyma. In addition to abnormalities of hepatic sinusoids, capable of taking up of Fe-TA NPs by hepatocytes is also critical implications for their accumulation and MRI enhancement efficiency.…”

The Role of Sinusoidal Endothelial Cells in the Axis of Inflammation and Cancer Within the Liver

“…Following production of substantial basement membrane, the phenotypic alterations in LSEC become virtually irreversible. Capillarisation is analogous with endothelial dysfunction, in which LSEC can no longer maintain HSC quiescence in response to shear stress signals ( Deleve et al, 2008 ; Xie et al, 2012 ), and together these processes precede fibrosis ( Horn et al, 1987 ; Fraser et al, 1991 ; Pasarín et al, 2012 ; Baiocchini et al, 2019 ). A recent study, however, showed that LSEC dysfunction and loss of fenestrations following chronic metabolic stress do not always go hand in hand ( Kus et al, 2019 ).…”

“…It is well-documented that fenestrations are altered in pathophysiological conditions ( Horn et al, 1987 ; Clark et al, 1988 ; Fraser et al, 1991 ; Xu et al, 2003 ; Baiocchini et al, 2019 ). Fenestrations also decrease with age ( Ito et al, 2007 ), a process dependent on p53 and p19 ARF - dependent signalling ( Koudelkova et al, 2015 ) which is associated with pseudocapillarisation, sinusoidal dysfunction, loss of vasodilatory capacity, and increased hepatic vascular resistance ( Dg et al, 2007 ; Jamieson et al, 2007 ; Maeso-Diaz et al, 2018 ).…”

SARS-CoV-2 cytopathogenesis in cultured cells and in COVID-19 autoptic lung, evidences of lipid involvement.

“…Samples were then dehydrated in graded ethanol and embedded in Epon resin, as previously described [14,15]. Ultrathin sections were stained with 2% uranyl acetate and observed under a transmission electron microscope JEOL JEM 2100 Plus (Japan Electron Optics Laboratory Co. Ltd. Tokyo, Japan).…”