In the present study, we examined the potential Galunisertib research buy contribution of portal myofibroblasts (PMF) to the vascular changes leading to cirrhosis. The analyses of liver cells based on the transcriptome of rat PMF compared to hepatic stellate cell-derived myofibroblasts in culture, identified COL15A1 as a marker of PMF. Normal liver contained rare COL15A1-immunoreactive cells adjacent to the bile ducts and canals of Hering in the portal area. A marked increase in COL15A1 expression occurred together with that of the endothelial cell marker vWF, in human and rat liver tissue, at advanced stages of fibrosis caused by either biliary or hepatocellular injury. In cirrhotic liver, COL15A1-expressing PMF adopted

a perivascular distribution outlining vascular capillaries proximal to reactive ductules, within large fibrotic septa. The effect of

PMF on endothelial cells was evaluated by in vitro and in vivo angiogenesis assays. PMF-conditioned medium increased the migration and tubulogenesis of liver endothelial cells and human umbilical vein endothelial cells, and triggered angiogenesis within Matrigel plugs in mice. In co-culture, PMF developed intercellular junctions with endothelial cells and enhanced the formation of vascular selleck chemical structures. PMF released VEGFA-containing microparticles, which activated VEGFR-2 in endothelial cells and largely mediated their proangiogenic effect. Cholangiocytes potentiated the angiogenic properties of PMF by increasing VEGFA expression and microparticle shedding in these cells. In conclusion, PMF are key cells in hepatic vascular remodeling. They signal to endothelial cells via VEGFA-laden microparticles and act as mural cells for newly formed vessels, driving scar progression from portal tracts into the parenchyma. (Hepatology 2014;) “
“Routine monitoring of liver tests throughout the early and late period following liver transplant is essential in detecting liver allograft injury. Causes of abnormal liver tests after transplant can be related to allograft integrity (primary graft non-function, delayed graft function), vascular problems (hepatic artery thrombosis, outflow obstruction), biliary MCE problems

(bile leak, biliary strictures), infections, immune reactions (acute or chronic rejection, autoimmune hepatitis), and recurrent disease (particularly hepatitis C). Ultrasound of the liver with Doppler examination of the hepatic artery is usually the first step in assessing abnormal tests and may detect biliary abnormalities and/or impaired hepatic artery flow. If the clinical suspicion for a biliary or vascular problem remains high despite a normal ultrasound then magnetic resonance cholangiopancreatography or angiography may be more sensitive. Liver biopsy is essential in making the diagnosis of rejection or recurrent disease. Interpretation of biopsy findings by a skilled pathologist is essential to establishing a correct diagnosis.