fibrin and Hyperemia

Chronic passive hepatic congestion (congestive hepatopathy) leads to hepatic fibrosis; however, the mechanisms involved in this process are not well understood. We developed a murine experimental model of congestive hepatopathy through partial ligation of the inferior vena cava (pIVCL). C57BL/6 and transgenic mice overexpressing tissue factor pathway inhibitor (SM22α-TFPI) were subjected to pIVCL or sham. Liver and blood samples were collected and analyzed in immunohistochemical, morphometric, real-time polymerase chain reaction, and western blot assays. Hepatic fibrosis and portal pressure were significantly increased after pIVCL concurrent with hepatic stellate cell (HSC) activation. Liver stiffness, as assessed by magnetic resonance elastography, correlated with portal pressure and preceded fibrosis in our model. Hepatic sinusoidal thrombosis as evidenced by fibrin deposition was demonstrated both in mice after pIVCL as well as in humans with congestive hepatopathy. Warfarin treatment and TFPI overexpression both had a protective effect on fibrosis development and HSC activation after pIVCL. In vitro studies show that congestion stimulates HSC fibronectin (FN) fibril assembly through direct effects of thrombi as well as by virtue of mechanical strain. Pretreatment with either Mab13 or Cytochalasin-D, to inhibit β-integrin or actin polymerization, respectively, significantly reduced fibrin and stretch-induced FN fibril assembly.. Chronic hepatic congestion leads to sinusoidal thrombosis and strain, which in turn promote hepatic fibrosis. These studies mechanistically link congestive hepatopathy to hepatic fibrosis.

Topics: Actins; Adult; Aged; Animals; Anticoagulants; Case-Control Studies; Cells, Cultured; Disease Models, Animal; Female; Fibrin; Fibronectins; Hepatic Stellate Cells; Humans; Hyperemia; Ligation; Liver Circulation; Liver Cirrhosis; Male; Mice, Inbred C57BL; Mice, Transgenic; Middle Aged; Thrombosis; Vena Cava, Inferior; Young Adult

Topics: Actins; Animals; Female; Fibrin; Humans; Hyperemia; Liver Cirrhosis; Male; Thrombosis

Topics: Blood Proteins; Capillaries; Capillary Permeability; Fibrin; Fibrinolysis; Humans; Hyperemia; Hypoxia; Leg; Rheology; Varicose Ulcer; Veins; Venous Insufficiency; Venous Pressure

This study was undertaken to differentiate between the morphological changes produced in chambered rat gastric mucosae by 40% ethanol and by 50 mM HCl. 40% ethanol produced both focal mucosal hyperemia and widespread exfoliation of the surface epithelium. Massive release of mucus accompanied both events. In the absence of acid the released mucus was stabilized by a network of fibrin, and epithelial continuity was re-established over non-hyperemic regions by migration of epithelial (and parietal) cells from the gastric pits. Hemorrhagic erosions occurred only in the presence of acid, but were limited to the hyperemic regions. Acid had the following effects: (1) platelet thrombi were destroyed, thus promoting hemorrhage; (2) destruction of the fibrin network by acid caused dissipation of the adherent mucous coat; (3) vulnerable cells which had previously shown only ischemic damage were irreversibly damaged by acid; (4) exposed basal lamina was destroyed, thus removing the substratum necessary for orderly epithelial re-establishment.

Topics: Acids; Animals; Blood Platelets; Ethanol; Female; Fibrin; Gastric Mucosa; Hyperemia; Microscopy, Electron; Rats; Stomach Diseases

Topics: Animals; Aqueous Humor; Basement Membrane; Biological Transport; Capillary Permeability; Carbon; Ciliary Body; Endotoxins; Epithelium; Escherichia coli; Female; Fibrin; Hyperemia; Iris; Male; Microscopy, Electron; Rabbits; Serum Albumin, Radio-Iodinated; Time Factors; Uveitis, Anterior