elastin and Liver-Cirrhosis

Metabolic-Associated Fatty Liver Disease (MAFLD) is a major cause of liver diseases globally and its prevalence is expected to grow in the coming decades. The main cause of MAFLD development is changed in the composition of the extracellular matrix (ECM). Increased production of matrix molecules and inflammatory processes lead to progressive fibrosis, cirrhosis, and ultimately liver failure. In addition, increased accumulation of sphingolipids accompanied by increased expression of pro-inflammatory cytokines in the ECM is closely related to lipogenesis, MAFLD development, and its progression to fibrosis. In our work, we will summarize all information regarding the role of sphingolipids e.g., ceramide and S1P in MAFLD development. These sphingolipids seem to have the most significant effect on macrophages and, consequently, HSCs which trigger the entire cascade of overproduction matrix molecules, especially type I and III collagen, proteoglycans, elastin, and also tissue inhibitors of metalloproteinases, which as a result cause the development of liver fibrosis.

Topics: Ceramides; Cytokines; Elastin; Extracellular Matrix; Fibrosis; Humans; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Proteoglycans; Sphingolipids

Liver fibrosis is a serious complication of schistosomiasis infection, is associated with increased amounts of collagen and the collagen cross-link, pyridinoline. Non-invasive markers of liver fibrosis have been developed. Serum and urinary markers of collagen synthesis and degradation have been studied to assess the balance between collagen synthesis, measured with markers of collagen synthesis such as amino-terminal propeptide of type III procollagen (PIIINP), and markers of degradation such as pyridinoline or pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP). It has been shown that mice infected with Schistosomiasis mansoni excrete excess pyridinoline cross links in urine and this was correlated with the collagen content of granulomas from the liver. Treatment of infected mice with an anti-parasitic drug, praziquantel, decreased the collagen content of parenchyma and excretion of pyridinoline in the urine. Although the connective tissue protein, elastin, is present in the liver, the role of elastin in liver fibrosis has not been investigated. However, it has been shown that the urinary concentration of elastin specific crosslinks, desmosine and isodesmosine, as well as the urinary concentration of the collagen crosslink, pyridinoline, correlated well with liver fibrosis score in biopsy specimens from patients with liver disease secondary to hepatitis C virus and alcohol. Each biopsy specimen was reviewed by two pathologists who were blinded as to the clinical data. The pathological evaluation generated scores for both inflammation and fibrosis. No correlation was seen between the urinary markers and inflammation scores. The measurement of non-invasive markers of collagen synthesis and degradation may be useful in monitoring the reversal of fibrosis following therapeutic intervention in schistosome infections.

Topics: Amino Acids; Animals; Biomarkers; Collagen; Desmosine; Elastin; Humans; Isodesmosine; Liver Cirrhosis; Schistosomiasis

The histological distinction between acute and chronic liver injury is a challenging aspect of liver histopathology. It is traditionally based on the interpretation of morphological changes to the extracellular matrix (ECM) at sites of hepatocyte loss using histochemical stains. Our aim was to investigate whether immunohistochemistry and multiplexing for collagen type (I & III) and elastic fibres and a modified Victoria blue method could be helpful. We studied 43 livers removed at transplantation for acute liver failure (ALF, 20 cases) or cirrhosis (23) plus 8 normal controls. In ALF the periportal ECM was normal in 2 cases, contained mainly collagen I associated with a ductular reaction in 6 cases, and delicate elastic strands in 11 cases. Periportal deposition of mainly collagen I and mature elastic fibres was observed in cirrhosis. In ALF the perisinusoidal ECM was intact in 4 cases, collapsed or condensed but of normal composition (predominantly collagen III) in 2 cases, and collapsed and condensed containing mostly collagen I in 17 cases (7 including delicate immature elastic strands). In contrast, bridging fibrous septa of cirrhosis contained abundant collagen 1 and bundles of mature elastin. We propose the use of a scale and the use of immunohistochemistry and multiplexing in additional to histochemical stains to characterise the ECM changes in acute and chronic liver injury.

Topics: Adult; Collagen; Elastic Tissue; Elastin; Extracellular Matrix; Female; Hepatocytes; Humans; Immunohistochemistry; Liver Cirrhosis; Liver Failure, Acute; Male; Retrospective Studies; Young Adult

Elastin is an amorphous protein highly resistant to elastase degradation and is believed to be the most stable component among the extracellular matrix (ECM) members. Thus the excessive deposition of elastin in advanced liver fibrosis may contribute to the declining reversibility of the disease. Our previous study has found that elastin crosslinking inhibition can effectively arrest liver fibrosis progression. To further understand the roles of elastin involved in liver fibrosis, we systematically investigated the expression, accumulation, and degradation based on dynamic and bidirectional CCl

Topics: Animals; Carbon Tetrachloride Poisoning; Collagen; Elastin; Gene Expression Regulation; Hepatocytes; Humans; Imaging, Three-Dimensional; Liver Cirrhosis; Mice; Tropoelastin

The aim of this study was to determine if elastin content in needle core native liver biopsies was predictive of clinical outcome in patients with chronic hepatitis C virus-related chronic liver disease.. Elastin contents in liver biopsies were determined by image analysis, technically validated in an independent centre, and correlated with outcome in patients with advanced (Ishak stage ≥5) chronic hepatitis C virus-related chronic liver disease. Elastin was robustly quantified in an operator-independent and laboratory-independent manner, with very strong correlation of elastin staining measured with two methods of image classification (r. We describe a simple and reproducible method for elastin quantification in liver biopsies that provides potentially valuable prognostic information to inform clinical management.

Topics: Adult; Biopsy, Large-Core Needle; Elastin; Female; Hepatitis C, Chronic; Humans; Liver Cirrhosis; Male; Middle Aged

The fibrosis stage, which is evaluated by the distribution pattern of collagen fibers, is a major predictor for the development of hepatocellular carcinoma (HCC) for patients with hepatitis C. Meanwhile, the role of elastin fibers has not yet been elucidated. The present study was conducted to determine the significance of quantifying both collagen and elastin fibers.. We enrolled 189 consecutive patients with hepatitis C and advanced fibrosis. Using Elastica van Gieson-stained whole-slide images of pretreatment liver biopsies, collagen and elastin fibers were evaluated pixel by pixel (0.46 μm/pixel) using an automated computational method. Consequently, fiber amount and cumulative incidences of HCC within 3 years were analyzed.. There was a significant correlation between collagen and elastin fibers, whereas variation in elastin fiber was greater than in collagen fiber. Both collagen fiber (p = 0.008) and elastin fiber (p < 0.001) were significantly correlated with F stage. In total, 30 patients developed HCC during follow-up. Patients who have higher elastin fiber (p = 0.002) in addition to higher collagen fiber (p = 0.05) showed significantly higher incidences of HCC. With regard to elastin fiber, this difference remained significant in F3 patients. Furthermore, for patients with a higher collagen fiber amount, higher elastin was a significant predictor for HCC development (p = 0.02).. Computational analysis is a novel technique for quantification of fibers with the added value of conventional staging. Elastin fiber is a predictor for the development of HCC independently of collagen fiber and F stage.

Topics: Aged; Carcinoma, Hepatocellular; Collagen; Elastin; Female; Hepatitis C, Chronic; Humans; Incidence; Liver; Liver Cirrhosis; Liver Neoplasms; Male; Middle Aged; Risk Factors

Progressive fibrosis increases hepatic resistance and causes portal hypertension with complications. During progressive fibrosis remodeling and deposition of collagens and elastin occur. Elastin remodeling is crucially involved in fibrosis progression in animal models and human data. This study investigated the association of circulating elastin with the clinical outcome in cirrhotic patients with severe portal hypertension receiving transjugular intrahepatic porto-systemic shunt (TIPS).. We analyzed portal and hepatic venous samples of 110 cirrhotic patients obtained at TIPS insertion and 2 weeks later. The circulating levels of elastin fragments (ELM) were determined using specific monoclonal ELISA. The relationship of ELM with clinical short-time follow-up and long-term outcome was investigated.. Circulating levels of ELM showed a gradient across the liver before TIPS with higher levels in the hepatic vein. Interestingly, the circulating ELM levels remained unchanged after TIPS. The circulating levels of ELM in portal and hepatic veins correlated with platelet counts and inversely with serum sodium. Hepatic venous levels of ELM were higher in CHILD C compared to CHILD A and B and were associated with the presence of ascites. Patients with high levels of ELM in the hepatic veins before TIPS showed poorer survival. In multivariate analysis ELM levels in the hepatic veins and MELD were independent predictors of mortality in these patients.. This study demonstrated that circulating levels of ELM are not associated with hemodynamic changes, but might reflect fibrosis remodeling and predict survival in patients with severe portal hypertension receiving TIPS independently of MELD.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Elastin; Enzyme-Linked Immunosorbent Assay; Female; Hemodynamics; Hepatorenal Syndrome; Humans; Hypertension, Portal; Kaplan-Meier Estimate; Kidney Function Tests; Liver Circulation; Liver Cirrhosis; Liver Function Tests; Male; Middle Aged; Multivariate Analysis; Peptide Fragments; Portal Vein; Portasystemic Shunt, Transjugular Intrahepatic; Predictive Value of Tests; Proportional Hazards Models; Risk Factors; Severity of Illness Index; Time Factors; Treatment Outcome

Combined antiretroviral therapy (cART) attenuates hepatic fibrosis in hepatitis C virus and HIV coinfected patients. However, the role of HIV or cART on hepatic fibrosis in HIV monoinfection is discussed controversially. During liver fibrosis, matrix metalloproteinases (MMPs) degrade extracellular matrix (ECM) proteins into small soluble fragments, which reflect hepatic remodeling processes. This study used these novel biomarkers to investigate the effect of HIV and cART on hepatic fibrosis remodeling.. In 249 patients with HIV monoinfection and 55 healthy controls, the serum levels of MMP-degraded collagen type III (C3M), biglycan (BGM), elastin (ELM), as well as the formation marker 7S (P4NP 7S), and MMP-degraded collagen type IV (C4M) were determined using specific ELISAs. Sixty-eight patients underwent a follow-up visit 3 years later including assessment of ECM markers and fibrosis using transient elastography (Fibroscan).. C3M, BGM, C4M and P4NP 7S were significantly elevated in HIV patients compared to controls and correlated to HIV viral loads and inversely to cART duration. C4M, P4NP 7S and ELM were lower in patients under cART therapy and in patients without HIV viremia, indicating that lowering of the HIV load by cART attenuates remodeling of ECM. The levels of C3M, C4M, P4NP 7S and ELM correlated significantly with the progression of fibrosis in these patients.. Specific therapy of patients with HIV monoinfection also beneficially influences liver fibrosis. These novel markers of liver fibrosis remodeling may help to monitor the hepatic effects by HIV therapy.

Topics: Adult; Antiviral Agents; Biglycan; Biomarkers; Coinfection; Collagen Type III; Cross-Sectional Studies; Disease Progression; Drug Therapy, Combination; Elasticity Imaging Techniques; Elastin; Extracellular Matrix; Female; Follow-Up Studies; Hepatitis C; HIV Infections; Humans; Liver Cirrhosis; Longitudinal Studies; Male; Middle Aged; Peptide Mapping

Results of investigation of collagen metabolism in Dupuitren's contracture (DC) were summarized. The patients were operated for calculous cholecystitis and DC stages II - III. The changes revealed witnessed about more expressed degradation of collagen and affection of the elastin components of connective tissue. On background of the pathological process progress in palmar aponeurosis in patients, suffering DC, a content of oxyproline have enhanced trustworthy in urine and reduced in tissue of a changed palmar aponeurosis.

Topics: Aged; Amino Acids; Cholecystitis; Collagen; Connective Tissue; Dupuytren Contracture; Elastin; Fascia; Humans; Hydroxyproline; Liver Cirrhosis; Male; Middle Aged; Severity of Illness Index

Histological evaluation of fibrosis after a liver biopsy is crucial for evaluating the pathology of patients with chronic liver disease. Previous studies have reported quantitative analyses of fibrosis using images of collagen-stained sections. However, analysis of these studies requires manual selection of the region of interest. In addition, the quantification of elastic fibers is not considered. The present study was conducted in order to measure both the collagen and elastic fiber area ratios using Elastica van Gieson-stained whole-slide images (WSIs) of liver biopsy specimens. High-resolution WSIs provide precise color classification, enabling accurate detection of even fine collagen and elastic fibers. To minimize the influence of pre-existing fibrous tissue, median area ratios of the collagen and elastic fibers were independently calculated from the image tiles of the WSIs. These median area ratios were highly concordant with area ratios after the pre-existing fibrous tissues were manually trimmed from the WSI. Further, these median area ratios were correlated with liver stiffness as measured by transient elastography (collagen: r = 0.73 [P < 0.01], elastic: r = 0.53 [P < 0.01]). Our approach to quantifying liver fibrosis will serve as an effective tool to evaluate liver diseases in routine practice.

Topics: Biopsy; Collagen; Coloring Agents; Elastic Tissue; Elasticity Imaging Techniques; Elastin; Hepatitis, Viral, Human; Humans; Image Processing, Computer-Assisted; Liver; Liver Cirrhosis; Severity of Illness Index

Hepatoportal sclerosis accompanied by dense elastic fibre deposition is generally regarded as the primary lesion in the development of idiopathic portal hypertension (IPH). This study was performed to clarify the mechanism of elastic fibre deposition in the peripheral portal tracts of IPH liver in relation to serum anti-endothelial cell antibodies (AECA). In-vitro experiments were performed using human dermal microvascular endothelial cells (HMVEC) and patients' sera. The presence of serum AECA was assayed by a cell-based enzyme-linked immunosorbent assay (ELISA) using HMVEC. Immunohistochemical analysis of elastin was performed using liver tissue sections of IPH patients. IPH sera contained one or more AECA that could bind to the vascular endothelial cells of the peripheral portal tracts of the liver. When the value of AECA greater than the mean ± 2 standard deviations of healthy controls was regarded as positive, the positive detection rate of either immunoglobulin (Ig)G, IgA or IgM AECA in IPH sera was 30% (10 of 33 cases). IPH sera induced the expression of elastin in HMVEC, which appeared to be associated with the presence of AECA. Apoptosis was also induced in HMVEC by the stimulation with IPH sera. In vivo, elastin expression was observed in the endothelial cells of the peripheral portal tracts of IPH livers in a proportion of cases. The disease pathogenesis of IPH seems to be heterogeneous, and this study elucidated a possible contribution of the induction of elastin expression in the portal vessels to hepatoportal sclerosis of IPH, which might be linked to serum AECA as a causative factor.

Topics: Apoptosis; Autoantibodies; Base Sequence; Case-Control Studies; Cells, Cultured; DNA Primers; Elastin; Endothelial Cells; Humans; Hypertension, Portal; Idiopathic Noncirrhotic Portal Hypertension; Immunohistochemistry; In Vitro Techniques; Liver Cirrhosis; Pancytopenia; Portal Vein; RNA, Messenger; Sclerosis; Splenomegaly

Focal zones of hepatic necrosis alternating with nodular regeneration in severe, acute to subacute hepatitis can be difficult to differentiate histologically from established cirrhosis, and diagnostic errors can result in incorrect patient management. Thus, an easily applicable, well-defined histologic method for differentiating these two lesions would be useful.. We examined trichrome (TRI), reticulin (RETIC), Verhoeff's elastic (VE), and orcein (ORC) stains on 13 cases of hepatic necrosis with regenerative nodules and 10 cases of end-stage cirrhosis to evaluate their utility for this problem.. Zones of recent necrosis in all severe hepatitis cases stained paler blue or pink, respectively, with TRI and VE than the established scar in cirrhosis or residual normal portal zones/central vein walls. With VE and ORC, elastic fibres were not seen in the necrotic zones of severe hepatitis, but were present in all cirrhotic livers. RETIC outlined the residual cell plate architecture in necrotic areas but had indistinct staining in fibrotic areas. The combination of the RETIC, TRI and ORC distinguished hepatic necrosis with regenerative nodules from nodules in the scar of established cirrhosis in 100% of the cases examined.. We conclude that this trio of special stains can be helpful adjuncts for this diagnostic problem.

Topics: Adult; Aged; Collagen; Coloring Agents; Diagnosis, Differential; Elastin; Female; Humans; Liver; Liver Cirrhosis; Male; Massive Hepatic Necrosis; Middle Aged; Reticulin

Myofibroblasts derived from portal fibroblasts are important fibrogenic cells in the early stages of biliary fibrosis. In contrast to hepatic stellate cells, portal fibroblasts have not been well studied in vitro, and little is known about their myofibroblastic differentiation. In this article we report the isolation and characterization of rat portal fibroblasts in culture. We demonstrate that primary portal fibroblasts undergo differentiation to alpha-smooth muscle actin-expressing myofibroblasts over 10-14 days. Marker analysis comparing portal fibroblasts to hepatic stellate cells demonstrated that these are distinct populations and that staining with elastin and desmin can differentiate between them. Portal fibroblasts expressed elastin at all stages in culture but never expressed desmin, whereas hepatic stellate cells consistently expressed desmin but never elastin. Immunostaining of rat liver tissue confirmed these results in vivo. Characterization of portal fibroblast differentiation in culture demonstrated that these cells required transforming growth factor-beta (TGF-beta): cells remained quiescent in the presence of a TGF-beta receptor kinase inhibitor, whereas exogenous TGF-beta1 enhanced portal fibroblast alpha-smooth muscle actin expression and stress fiber formation. In contrast, platelet-derived growth factor inhibited myofibroblastic differentiation. Portal fibroblasts were also dependent on mechanical tension for myofibroblastic differentiation, and cells cultured on polyacrylamide supports of variable stiffness demonstrated an increasingly myofibroblastic phenotype as stiffness increased.. Portal fibroblasts are morphologically and functionally distinct from hepatic stellate cells. Portal fibroblast myofibroblastic differentiation can be modeled in culture and requires both TGF-beta and mechanical tension.

Topics: Actins; Animals; Biomechanical Phenomena; Cell Adhesion; Cell Differentiation; Cell Proliferation; Cells, Cultured; Disease Models, Animal; Elastin; Fibroblasts; Hepatocytes; Liver Cirrhosis; Male; Platelet-Derived Growth Factor; Rats; Rats, Sprague-Dawley; Transforming Growth Factor beta1; Vitamin A

Fibrillin-1, together with elastin, is the main component of elastic fibers found throughout the extracellular space and responsible for the biomechanical properties of most tissues and organs. In this work, fibrillin-1 expression and modulation were explored in experimental rat liver fibrosis and in vitro; furthermore, the role of fibrillin-1 fragments on cell adhesion was analyzed. Fibrosis was induced by subjecting rats to common bile duct ligation for 72 h and 7 days or carbon tetrachloride (CCl(4)) treatment for 2 and 6 weeks. Immunohistochemistry showed that, after bile duct ligation, fibrillin-1, elastin, and alpha-smooth muscle actin colocalized in the developing portal connective tissue. In CCl(4)-treated animals, a similar colocalization was observed in septa; however, elastin deposition was not observed around activated alpha-smooth muscle actin-positive stellate cells of the parenchyma. Treatment with the profibrogenic mediator transforming growth factor-beta1 (TGF-beta1) greatly increased the fibrillin-1 expression of cultured liver fibroblasts. The level of fibrillin-1 expression was significantly higher in cells grown in restrained (stressed) collagen lattices compared with those grown in unrestrained collagen lattices. Cell adhesion on the C-terminal fragment of fibrillin-1 containing the RGD sequence (rF6H) slightly increased (between 0.3 and 2.5 microg/ml) and decreased at higher concentrations, while adhesion on the N-terminal fragment of fibrillin-1 (rF16) was dose-dependently decreased. In addition, the rF16 fragment decreased cell adhesion to fibronectin. In conclusion, our study illustrates the important deposition of fibrillin-1 that occurs in two mechanistically distinct settings of liver fibrogenesis. Furthermore, the induction of fibrillin-1 expression by TGF-beta1 and mechanical stress, and the antiadhesive properties of fibrillin-1 fragments suggest important implications for physiological and pathological fibrillin-1 catabolism during tissue remodeling.

Topics: Actins; Animals; Cell Adhesion; Cell Line, Transformed; Collagen; Elastic Tissue; Elastin; Fibrillin-1; Fibrillins; Fibroblasts; Humans; Immunoenzyme Techniques; Isometric Contraction; Liver; Liver Cirrhosis; Male; Microfibrils; Microfilament Proteins; Rats; Rats, Sprague-Dawley; Stress, Mechanical; Transforming Growth Factor beta; Transforming Growth Factor beta1

The expression and the distribution of fibrillin-1 and elastin were studied in normal and pathological human liver samples.. As controls, histologically normal/subnormal liver samples (n = 24) were used. Pathological samples corresponded to seven cirrhosis and eight hepatocellular carcinomas (HCC) developed on cirrhotic (four) or noncirrhotic (four) liver.. In normal liver, fibrillin-1 and elastin co-localized in vessel walls and portal tract connective tissue. Fibrillin-1 alone was detected along sinusoids and in portal spaces at the interface with the limiting hepatocytic plates and close to the basement membrane of bile ducts. By transmission electron microscopy, typical bundles of microfibrils were detected both in Disse space and in portal zones. Cirrhotic nodules were usually rich in fibrillin-1 along sinusoids; fibrillin-1 and elastin were co-localized in fibrotic septa surrounding nodules. In HCC, fibrillin-1 was present between tumoral hepatocytes; stromal reaction around the tumors contained both fibrillin-1 and elastin.. Fibrillin-1 was associated with elastin in portal mesenchyme and vessel walls of normal liver, in fibrotic septa around cirrhotic nodules and stromal reaction around HCC, but was expressed alone in the perisinusoidal space. The functional roles for fibrillin-1 in non-elastic tissues, such as the liver, remain to be elucidated.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Hepatocellular; Elastin; Female; Fibrillin-1; Fibrillins; Humans; Liver; Liver Cirrhosis; Liver Neoplasms; Male; Microfilament Proteins; Middle Aged; Reference Values; Tissue Distribution

The network of elastic system fibers in human fibrotic liver was investigated by histological methods, immunohistochemical staining, and electron microscopy. Type III collagen was seen not only in regions of portal fibrosis but also in the sinusoidal wall. However, elastic system fibers were not found in the Disse space of the sinusoidal wall. Elastic system fibers including oxytalan, elaunin, and elastic fibers were found successively in the course of elastogenesis. A few normal oxytalan fibers and abnormal oxytalan fibers were observed in the periportal tracts. Few normal elaunin and abnormal elaunin fibers were observed in regions of portal fibrosis but not in the surrounding margin. Elastic fibers, only in scarce amounts, were observed around the portal veins in the case of chronic active hepatitis but not in acute hepatitis. Abnormal oxytalan fibers were seen as a bundle of wavelike microfibrils and had an irregular arrangement. Abnormal elaunin fibers were not associated with bundles of microfibrils. Abnormal elaunin fibers in large amounts were found interspersed with spiraled collagen, which most likely indicates that the oxytalan fibers degenerated in the course of elastogenesis. Thus, in a fibrotic liver it is possible that synthesis of normal elaunin and elastic fibers does not occur or that the quantity of such fibers synthesized may be small because of the effect of the degenerated oxytalan fibers. As a characteristic of liver fibrosis, the composition of abnormal elastic system fibers and spiraled collagen differs from that in other fibrotic organs.

Topics: Adult; Aged; Collagen; Contractile Proteins; Elastic Tissue; Elastin; Extracellular Matrix Proteins; Female; Humans; Immunohistochemistry; Liver; Liver Cirrhosis; Male; Microscopy, Electron; Middle Aged

We have isolated a mouse lysyl oxidase-like (LOXL) cDNA from a mouse embryo cDNA library and used this cDNA to measure changes in steady state levels of LOXL mRNA during the development of carbon tetrachloride-induced liver fibrosis in adult mice. These results revealed the coincident appearance of increased steady state levels of LOXL mRNA and type III procollagen mRNA early in the development of liver fibrosis. In contrast, steady state levels of lysyl oxidase mRNA increased throughout the onset of hepatic fibrosis and appeared in parallel with the increased steady state levels of pro-alphaI (I) collagen mRNA. These findings suggest that the LOXL protein (possibly an isoform of lysyl oxidase) is involved in the development of lysine-derived cross-links in collagenous substrates. Moreover, the substrate specificity of the LOXL protein may be different to that of lysyl oxidase and this difference may be collagen-type specific.

Topics: Animals; Base Sequence; Blotting, Northern; Carbon Tetrachloride; Dose-Response Relationship, Drug; Elastin; Gene Expression; Gene Library; Humans; Immunohistochemistry; Liver; Liver Cirrhosis; Liver Cirrhosis, Experimental; Male; Mice; Molecular Sequence Data; Procollagen; Protein-Lysine 6-Oxidase; RNA; Sequence Analysis, DNA

Human liver tissue obtained at autopsy was extracted with hot 0.1 M NaOH. Determination of amino acids desmosine and isodesmosine was used to quantify elastin in the insoluble residue. Hydroxyproline content was used as an index of collagen content in the liver. Hydroxyproline content was twofold in fibrotic liver and threefold in cirrhotic liver when compared to normal liver, while the sum of desmosine and isodesmosine increased threefold and sixfold, respectively. Elastin content is low in normal liver when compared to collagen but appears to grow much faster in diseased liver.

Topics: Aged; Elastin; Humans; Liver; Liver Cirrhosis; Middle Aged

Increased elastic stained material has been described in fibrotic and cirrhotic liver processes. The aim of this work was to follow the development and distribution of elastic fibers from 48 chronic alcoholic patients. Patients were scored for fibrosis as 0, without fibrosis or minimal (n = 5); 1, incipient or early fibrosis (n = 9); 2, fibrosis or incomplete cirrhosis (n = 12); and 3, cirrhosis (n = 22). Elastica staining was performed by orcein, resorcin-fuchsin and iron hematoxylin and confirmed by immunofluorescence staining with an anti-human elastin antibody (Institut Pasteur). Electron microscopy of representative cases of each group and electron microscopy of immunolabelled elastin (n = 5) were also performed. In early alcoholic fibrosis, oxytalan fibers were pointed out in terminal hepatic veins and in Disse space. In fibrous portal extensions and cirrhotic internodular septa, oxytalan and elaunin fibers represented the major elastin components in association with the alcoholic liver fibroplasia. Immunostaining with anti-elastin Ab exhibits the same distribution as with histochemical methods in portal and septal zones. Electron microscopy confirmed abundant microfibrillar bundles between collagen fibers that mesh and are in continuity with elaunin fibers. Immunoelectron microscopy confirmed elastin deposits in the amorphous material and in association with the microfibrillar material in the portal and septal zones and disclosed elastin even in the thin strands of fibrotic tissue. In conclusion, elastogenesis, mainly represented by oxytalan and elaunin fibers, develops in alcoholic disease and takes part, with collagen deposits, in the fibrotic process.

Topics: Collagen; Elastin; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Liver Circulation; Liver Cirrhosis; Liver Diseases, Alcoholic; Microscopy, Electron; Venules

Topics: Amino Acids; Animals; Aorta; Desmosine; Elastin; Humans; Liver; Liver Cirrhosis; Lung; Male; Rats; Rats, Inbred Strains

Topics: Animals; Collagen; Elastin; Hepatitis B; Hepatitis C; Humans; Liver Cirrhosis; Rats

Hepatic fibrosis was induced in rats by poisoning them with carbon tetrachloride. The influence of anti-inflammatory steroids (hydrocortisone, prednisone, dexamathasone) upon elastin content in liver was investigated in healthy and CCl4 intoxicated rats. An increase of liver elastin content was observed in animals with CCl4-induced hepatic fibrosis Opposite results were obtained in normal rats after treating them with glucocorticosteroids. A decrease of elastin content after steroid treatment was also found in rats with injured liver, as compared to animals receiving CCl4 only. Presumable mechanisms of the results are discussed.

Topics: Animals; Anti-Inflammatory Agents; Carbon Tetrachloride Poisoning; Elastin; Glucocorticoids; Liver; Liver Cirrhosis; Male; Rats; Rats, Inbred Strains

Histochemical studies by Sesta et al. (1965) demonstrated in hepatic cirrhosis an embryonic-type collagen that differs from reticulum fibers. Grimaud and coworkers observed type IV collagen in cirrhotic lesions. To determine whether or not this collagen can be visualized by light microscopy, sections fixed in Carnoy-type solutions were treated with the periodic acid -Na bisulfite - resorcin-fuchsin (PBRF) reaction for basement membranes. Reticulum and coarse (Type I) collagen fibers were visualized with picro-Sirius Red F3BA. In normal livers, basement membranes occurred only around bile ducts and blood vessels. In hepatic cirrhosis basement membrane-like material extended from septa into nodules. The reaction patterns were similar to immunofluorescence pictures of Type IV collagen. The ratios of different collagens varied widely and were apparently determined by type and of lesions and other factors. For further studies, improved light microscopic reactions are needed, especially for simultaneous demonstration of embryonic and basement membrane-type collagens in contrasting colors.

Topics: Collagen; Elastin; Fluorescent Antibody Technique; Humans; Liver; Liver Cirrhosis; Microscopy, Fluorescence

Elastin fibers formation was previously found to be an important feature of advanced human liver cirrhosis. Now it has been shown that chronic carbon tetrachloride administration to rats can be used to simulate this condition experimentally. Elastin fibers are found in the septa of connective tissue surrounding parenchymal nodules. Elastin content in liver measured as hydroxyproline insoluble in 0.1 N NaOH is increased about 3 times after a 4 month carbon tetrachloride treatment.

Topics: Animals; Carbon Tetrachloride Poisoning; Connective Tissue; Elastin; Hydroxyproline; Liver; Liver Cirrhosis; Male; Rats

Topics: Arteries; Chronic Disease; Collagen; Elastic Tissue; Elastin; Hepatitis; Humans; Liver; Liver Cirrhosis; Microscopy, Electron

Topics: Acromegaly; Adult; Collagen; Elastin; Hepatitis; Humans; Hyperthyroidism; Liver Cirrhosis; Liver Function Tests; Liver Neoplasms; Mercaptoethylamines; Monoamine Oxidase; Scleroderma, Systemic; Spectrophotometry

Topics: Collagen; Elastic Tissue; Elastin; Hepatitis; Humans; Liver; Liver Cirrhosis