Female ; Humans ; Hypertension, Portal ; etiology ; immunology ; Male ; Proliferating Cell Nuclear Antigen ; metabolism ; Spleen ; immunology ; metabolism ; pathology

Animals ; Hydrogen Sulfide ; metabolism ; Hypertension, Portal ; metabolism ; physiopathology ; Male ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo study the relationship between the dynamic changes of caveolin-1 with the degrees of liver fibrosis and portal venous pressure (PVP) in the process of rat liver cirrhosis formation induced by dimethylnitrosamine (DMN); also to investigate the mechanisms of caveolin-1 in the regulation of endothelial nitric oxide synthase (eNOS).

METHODSLiver cirrhosis was induced in rats by DMN. The degrees of liver fibrosis and PVP were measured. NOS activity was assessed by citrulline generation. Protein expressions of caveolin-1, eNOS and caveolin-1-eNOS interactions were examined by Western blot and immunoprecipitation, respectively.

RESULTSFour weeks after DMN administration, liver fibrosis was at its peak and then decreased gradually. Immunoprecipitation and Western blot demonstrated that there was enhanced binding of caveolin-1 with eNOS in the process of rat liver cirrhosis. An increase in caveolin-1 expression was detected but the expression of eNOS was lower in cirrhotic tissues than in normal liver tissues. Caveolin-1 protein levels were positively correlated with the degrees of liver fibrosis and the levels of PVP (r=0.967, P < 0.01; r=0.922, P < 0.01, respectively), while NOS catalytic activity was negatively correlated with the degrees of liver fibrosis and levels of PVP (r= 0.973, P < 0.01; r=-0.947, P < 0.01) respectively.

CONCLUSIONSCaveolin-1 upregulation is associated with the development of portal hypertension in liver cirrhosis. Over-expression of caveolin-1 in perisinusoidal cells may promote caveolin-1-eNOS binding and reduce the activity of eNOS.

Animals ; Caveolin 1 ; metabolism ; Hypertension, Portal ; metabolism ; Liver Cirrhosis, Experimental ; metabolism ; Nitric Oxide Synthase Type III ; metabolism ; Rats ; Rats, Wistar

The purpose of the present study was to assess the correlation that likely exists among increased portal pressure (Pp), portal blood flow quantity (Qp) and ETA and ETB receptor mRNA expression in human cirrhosis. In situ hybridization and reverse-transcription polymerase chain reactions (RT-PCR) were performed to determined the expression of ETA and ETB receptor mRNA in liver tissues from traumatic subjects (n = 10) and cirrhotic patients (n = 15) in whom hepatic hemodynamic values were measured. The expression of the two transcripts was significantly higher in liver samples of cirrhotic patients than in those obtained from traumatic subjects. It has shown that ETA receptor mRNA predominantly located in hepatic stellate cells (HSCs) and vascular smooth muscle cells of intrahepatic arteries and portal veins, ETB receptor mRNA in HSCs, sinusoidal endothelial cells and Kuppfer cells. There was a highly significant direct relationship between ETA and ETB receptor mRNA and Pp and Qp in cirrhotic patients. It suggests that liver paracrine endothelin system may be overactivated in human cirrhosis accompanied with increased expression of ETA and ETB receptor mRNA which may play an important role in the pathogenesis and maintenance of splanchnic hyperdynamics.
Female ; Gene Expression ; Hemodynamics ; Humans ; Hypertension, Portal ; metabolism ; Liver Cirrhosis ; genetics ; metabolism ; Male ; Portal Vein ; physiopathology ; Receptors, Endothelin ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Splanchnic Circulation ; physiology

Far Eastern countries including Korea show the high prevalence of hepatitis B virus carriers, so that the incidence of liver cirrhosis is higher than in western countries. But pregnancies with liver cirrhosis are rarely encountered in clinical settings, since liver cirrhosis usually develops after childbearing ages and often causes the disturbance of estrogen metabolism, resulting in severe menstrual irregularity and infertility. Therefore, little is known about the interactions between liver cirrhosis and pregnancy. Liver cirrhosis and portal hypertension are not contraindications to pregnancy but necessitate intensive monitoring throughout pregnancy because the complications of liver cirrhosis, which pose additional risks during pregnancy, are numerous and unpredictable. We report 3 cases of pregnancies in patients with liver cirrhosis with brief review of the literature.
Estrogens ; Hepatitis B virus ; Humans ; Hypertension, Portal ; Incidence ; Infertility ; Korea ; Liver Cirrhosis* ; Liver* ; Metabolism ; Pregnancy* ; Prevalence

Portal hypertension (PHT) is associated with changes in the intrahepatic, systemic and portosystemic collateral circulations. Alteration in vasoreactivity (vasodilation and vasoconstriction) plays a central role in the pathogenesis of PHT by contributing to increased intrahepatic resistance, hyperdynamic circulation and the expansion of the collateral circulation. PHT is also importantly characterized by changes in vascular structure; termed vascular remodeling, which is an adaptive response of the vessel wall that occurs in response to chronic changes in the environment such as shear stress. Angiogenesis, the sprouting of new blood vessels, also occurs in PHT, especially in the expansion of the portosystemic collateral circulation. These complementary processes of vasoreactivity, vascular remodeling and angiogenesis represent important targets in the research for the treatment of portal hypertension.
Collateral Circulation/physiology ; Endothelial Cells/metabolism ; Hepatic Stellate Cells/metabolism ; Humans ; Hypertension, Portal/*etiology ; Liver Circulation/physiology ; Vascular Resistance

Because of the anatomical position and its unique vascular system, the liver is susceptible to the exposure to the microbial products from the gut. Although large amount of microbes colonize in the gut, translocation of the microbes or microbial products into the liver and systemic circulation is prevented by gut epithelial barrier function and cleansing and detoxifying functions of the liver in healthy subjects. However, when the intestinal barrier function is disrupted, large amount of bacterial products can enter into the liver and systemic circulation and induce inflammation through their receptors. Nowadays, there have been various reports suggesting the role of gut flora and bacterial translocation in the pathogenesis of chronic liver disease and portal hypertension. This review summarizes the current knowledge about bacterial translocation and its contribution to the pathogenesis of chronic liver diseases and portal hypertension.
Antigens, CD14/metabolism ; Bacterial Translocation ; Gastrointestinal Tract/*microbiology ; Humans ; Hypertension, Portal/metabolism/*pathology ; Liver/metabolism/*microbiology ; Liver Cirrhosis/metabolism/*pathology ; Receptors, Cytoplasmic and Nuclear/metabolism ; Toll-Like Receptors/metabolism

Animals ; Blood Pressure ; physiology ; Hemodynamics ; physiology ; Hypertension, Portal ; blood ; metabolism ; physiopathology ; Liver Cirrhosis, Experimental ; blood ; metabolism ; physiopathology ; Male ; Neuropeptide Y ; blood ; metabolism ; Portal Pressure ; physiology ; Rats ; Rats, Sprague-Dawley ; Sodium ; urine

The purpose of the present study was to assess the correlation that likely exists among increased portal pressure (Pp), portal blood flow quantity (Qp) and ETA and ETB receptor mRNA expression in human cirrhosis. In situ hybridization and reverse-transcription polymerase chain reactions (RT-PCR) were performed to determined the expression of ETA and ETB receptor mRNA in liver tissues from traumatic subjects (n = 10) and cirrhotic patients (n = 15) in whom hepatic hemodynamic values were measured. The expression of the two transcripts was significantly higher in liver samples of cirrhotic patients than in those obtained from traumatic subjects. It has shown that ETA receptor mRNA predominantly located in hepatic stellate cells (HSCs) and vascular smooth muscle cells of intrahepatic arteries and portal veins, ETB receptor mRNA in HSCs, sinusoidal endothelial cells and Kuppfer cells. There was a highly significant direct relationship between ETA and ETB receptor mRNA and Pp and Qp in cirrhotic patients. It suggests that liver paracrine endothelin system may be overactivated in human cirrhosis accompanied with increased expression of ETA and ETB receptor mRNA which may play an important role in the pathogenesis and maintenance of splanchnic hyperdynamics.
Gene Expression ; Hemodynamic Processes ; Hypertension, Portal/metabolism ; Liver Cirrhosis/genetics ; Liver Cirrhosis/*metabolism ; Portal Vein/*physiopathology ; Receptors, Endothelin/genetics ; Receptors, Endothelin/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; *Splanchnic Circulation/physiology

OBJECTIVETo identify the differentially expressed genes associated with hypersplenism in patients with portal hypertension.

METHODSThe total RNA were extracted from the macrophages isolated from normal spleen and the spleen of patients with portal hypertension and reversely transcribed to cDNA with the incorporation of fluorescent (cy3 and cy5)-labeled dCTP to prepare the hybridization probes. After hybridization of Biostar-H140s chip containing 14,112 spots of cDNAs with the prepared probes, the gene chip was scanned for fluorescence intensity to screen the differently expressed genes. Three gene chips were used for hybridization and only the genes with differential expression in all the three chips were considered to associate with hypersplenism in patients with portal hypertension.

RESULTSTotaling 896, 1330 and 898 genes were identified to be differentially expressed by the three chips, respectively, and 121 genes (0.86%) showed differential expression in all the three chips, including 21 up-regulated known genes and 73 down-regulated known genes. The differently expressed genes were functionally related with ion channels and transport proteins, cyclins, cytoskeleton, cell receptors, cell signal transduction, metabolism, immunity, and so forth. These genes might be involved in hypersplenism in the condition of portal hypertension.

CONCLUSIONcDNA microarray-based screening of differentially expressed genes in the macrophages in the spleen may provide new insights into the pathogenesis of hypersplenism in patients with portal hypertension.

Female ; Gene Expression Profiling ; Humans ; Hypersplenism ; etiology ; genetics ; Hypertension, Portal ; complications ; genetics ; Macrophages ; metabolism ; Male ; Oligonucleotide Array Sequence Analysis ; methods ; Spleen ; metabolism ; pathology