Hepatic sinusoidal pseudocapillarization with aging in the non-human primate

Alterations in liver sinusoidal endothelium in a baboon model of type 1 diabetes

“…Although steatohepatitis was not observed, there was extensive perisinusoidal fibrosis and deposition of basal lamina, which was termed 'diabetic hepatosclerosis'. On the whole, our results of hepatosclerosis are consistent with these previous reports; however, we also noted extensive collagen deposition in the controls, which may reflect ageing changes in the baboon [6]. Hepatosclerosis is reported to be associated with microvascular complications of diabetes in other organ sites [26].…”

“…In the diabetic livers, the LSECs were found to be about 40% thicker and the porosity of fenestrations was reduced by about 50%. These are substantial changes and of a similar magnitude to those reported in old age [5][6][7][8]. In addition, diabetes was associated with increased endothelial production of von Willebrand factor and caveolin-1 and increased Masson's trichrome staining.…”

“…The remaining liver was perfusion-fixed for electron microscopy as previously published [6]. An aliquot (1-2 ml) of fixative (2% [w/v] glutaraldehyde/3% [w/v] paraformaldehyde in 0.1 mol/l sodium cacodylate buffer, 0.1 mol/ l sucrose, 2 mmol/l CaCl 2 ) was injected slowly into the liver sample using a 25G needle until the tissue hardened.…”

“…Of interest in diabetes mellitus is the observation that fenestrations in the LSECs appear to act as conduits for the transfer of some lipoproteins, especially chylomicron remnants, between the blood and hepatocytes [2,4]. In old age, a substantial loss of fenestrations in the LSECs occurs [5][6][7][8], which impairs lipoprotein transfer to the hepatocyte [9]. This provides a mechanism for age-related impairment in chylomicron remnant clearance and post-prandial hypertriacylglycerolaemia, thus possibly contributing to enhanced vascular risk among older people [4].…”

The size of sinusoidal fenestrae is a critical determinant of hepatocyte transduction after adenoviral gene transfer

“…Aging is also associated with hepatic pseudocapillarization. [36][37][38] The size of fenestrae may also be a determinant of hepatocyte transduction after transfer with retroviral or lentiviral vectors, which have a diameter between 126 and 133 nm. [39][40][41] A role of the size of fenestrae in the biodistribution of adenoviral vectors in the adrenal gland has been previously suggested by Wang et al 42 Systemic administration of adenoviral vectors in mice induced transgene expression in the adrenal gland that was comparable but somewhat lower than in the liver and predominant in the zona fasciculata, the part of the adrenal cortex with the largest diameter of fenestrae.…”