Portal hypertension-related inflammatory phenotypes: From a vitelline and amniotic point of view

Abstract

Prehepatic portal hypertension induces a splanchnic low-grade inflammatory response that could switch to high-grade inflammation with the development of severe and life-threatening complications when associated with chronic liver disease. The extraembryonic origin of the portal system maybe determines the regression to an extraembryonic phenotype, i.e., vitellogenic and amniotic, during the evolution of both types of portal hypertension. Thus, prehepatic portal hypertension, or compensated hypertension by portal vein ligation in the rat, is associated with molecular mechanisms related to vitellogenesis, where hepatic steatosis and splanchnic angiogenesis stand out. In turn, extrahepatic cholestasis in the rat induces intrahepatic portal hypertension, or decompensated hypertension, with ascites and hepatorenal syndrome. The splanchnic interstitium, the mesenteric lymphatic system, and the peritoneal mesothelium seem to create an inflammatory pathway that could have a key pathophysiological relevance in the production of ascites. The hypothetical comparison between the ascitic and the amniotic fluid also allows for translational investtigation. The induced regression of the splanchnic system to extraembryonic functions by portal hypertension highlights the great relevance of the extraembryonic structures even during post-natal life.

Embrionary way to create a fatty liver in portal hypertension

“…Moreover, the localization of the early inflammatory response could also favor the posterior storage of substances derived from the acute phase response[29]. Therefore, in the liver of the rats with prehepatic portal hypertension, the space of Disse could represent the anatomically definable compartment where the early inflammatory response is expressed (Figure 2).…”

“…Stress of the neuro-endocrine system by portal hypertension could be induce by three mechanisms: The hypothalamic-pituitary-adrenal axis, the sympathetic-adrenal medullary and the sympathetic nervous system[ 28 ] (Figure 2 ). Moreover, the localization of the early inflammatory response could also favor the posterior storage of substances derived from the acute phase response[ 29 ]. Therefore, in the liver of the rats with prehepatic portal hypertension, the space of Disse could represent the anatomically definable compartment where the early inflammatory response is expressed (Figure 2 ).…”

“…Regarding the ontogenic origin, the liver, and in particular the omentum, could be mimicking the yolk sac, in which pathological lipid deposition takes place. Under this scenario, the liver and the omentum would be regressing to evolutive phases with suitable metabolic conditions, supported by the expression of inflammatory markers such as tumor necrosis factor (TNF)-α, IL-6, C reactive protein and leptin[ 19 , 29 ]. In terms of phylogenetic approach, the body would be adopting the molecular mechanisms related to the vitellogenesis[ 53 , 54 ], in which oviparous species provide a glycolipoprotein yolk storage called vitelline to the egg as food-source for the embryo[ 54 ].…”