angiotensinogen and Liver-Diseases

alpha 1-Antitrypsin, alpha 1-antichymotrypsin and angiotensinogen are three genetically homologous acute phase reactants which belong to the super family of serine proteinase inhibitors (serpins). In this report the dissociate expression of these respective genes in various liver diseases or after exposure to estrogen is emphasized. In addition, the influence of abnormal genetic variants on plasma levels of these proteins and on liver cell function is discussed.

Topics: Acute-Phase Proteins; alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; alpha 1-Antitrypsin Deficiency; Angiotensinogen; Humans; Liver Diseases; Serpins

Renal tubular dysgenesis has been reported in isolated cases of neonatal hemochromatosis (NH). We hypothesized that fetal liver injury in NH impairs proximal renal tubular development via impaired hepatic angiotensinogen (AGT) elaboration. Morphometric analyses were performed of postmortem liver and kidney sections of cases of proven NH and postconception age-matched controls for renal proximal tubule density, hepatocyte mass, and hepatic AGT expression. Proximal tubule density was markedly reduced in NH cases, although they showed a spectrum from mild to severe paucity. Hepatic AGT expression was markedly reduced in NH cases and correlated closely with reduced hepatocyte mass. A linear relationship was established between hepatic AGT expression and the degree of renal tubular dysgenesis suggesting that there is a relationship between them. Our results demonstrate that there is a spectrum of kidney pathology in patients with NH including a large proportion of cases with severe proximal tubular dysgenesis. Hepatic synthetic failure resulting in insufficient production of AGT to support renal tubular development is the likely mechanism of kidney disease in NH.

Topics: Angiotensinogen; Autopsy; Case-Control Studies; Down-Regulation; Female; Gestational Age; Hemochromatosis; Humans; Immunohistochemistry; Kidney Tubules, Proximal; Liver; Liver Diseases; Pregnancy

Hepatic stellate cells express all components of the renin-angiotensinogen (AGT) system and secrete active angiotensin II. Animal studies provided evidence that angiotensin II stimulates the accumulation of extracellular matrix by enhancing transforming growth factor beta1 production. A functional genetic alteration in the human AGT promoter (c.1-44G>A) has been linked to accelerated progression of fibrosis in hepatitis C virus infection.. We enrolled 2154 patients with chronic liver disease of various etiologies, including 1286 individuals with chronic hepatitis C virus infection as well as 207 healthy volunteers. We performed genotyping for two AGT variants, c.1-44G>A and c.803T>C (p.M268T), by melting curve analysis using fluorescence resonance energy transfer probes.. Allele frequencies and genotype distributions of both variants did not differ between patients and controls. Genotype frequencies of the c.1-44G>A variant were GG 31.0%, GA 45.6%, and AA 23.4% in patients and GG 30.0%, GA 47.8%, and AA 22.2% in controls. The genotype frequencies of p.M268T, which is in strong linkage disequilibrium with c.1-44G>A, were MM 30.8%, MT 45.5%, and TT 23.4% in patients and MM 29.0%, MT 48.8%, and TT 22.2% in controls. Both variants were associated with neither higher stages of fibrosis nor requirement for liver transplantation in any of the diagnosis subgroups. Particularly, these genetic alterations were not associated with progressive fibrosis in chronic HCV infection.. In contrast to previous reports, both AGT variants do not predispose to the progression of fibrosis in chronic liver disease.

Topics: Adult; Aged; Aged, 80 and over; Alleles; Angiotensinogen; Case-Control Studies; Disease Progression; Female; Fibrosis; Gene Frequency; Genetic Variation; Genotype; Hepatic Stellate Cells; Hepatitis C, Chronic; Humans; Linkage Disequilibrium; Liver Diseases; Liver Diseases, Alcoholic; Male; Middle Aged; Risk Factors; Young Adult

The renin substrate angiotensinogen (AGT) belongs to a supergene family of proteins that also includes alpha 1-antitrypsin (AAT) and alpha 1-antichymotrypsin (ACT), acute-phase reactants with known serine proteinase inhibitory (serpin) function. AGT lacks a known inhibitory function but is an acute-phase reactant. In this study we have compared the plasma levels, as analysed by electroimmunoassay, of AGT with AAT in patients with different types of chronic liver disease. AAT levels are regularly elevated in liver disease patients in contrast to AGT, which remains normal until late in the disease course. The AGT levels (mean +/- SD) were: in alcoholic cirrhosis (n = 19) 100 +/- 27.3%, in chronic active hepatitis (n = 14) 100 +/- 23.2%, in primary biliary cirrhosis (n = 18) 106 +/- 26.1% and in non-alcoholic cirrhosis (n = 15) 92 +/- 38.4%. Only occasionally were levels less than 50% of normal seen. In general, AGT levels were unrelated to sex and type of underlying liver disease and did not correlate with degree of hepatocellular impairment. Crossed immunoelectrophoresis showed no abnormal charge heterogeneity of AGT in patients with low levels. Our data are consistent with a dissociate expression of the homologous serpin genes in chronic liver disease. We speculate that the magnitude of the dissociated response is influenced by hormonal factors.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; alpha 1-Antitrypsin; Angiotensinogen; Arthritis, Rheumatoid; Chronic Disease; Cross-Sectional Studies; Female; Humans; Immunochemistry; Immunoelectrophoresis, Two-Dimensional; Infant, Newborn; Liver Diseases; Longitudinal Studies; Male; Middle Aged

Arterial blood pressure, renal function and plasma concentrations of renin and renin substrate (angiotensinogen) were investigated in guinea pigs subjected to galactosamine-induced (1 g/kg i.v.) liver cell necrosis. Blood pressure declined continuously by 50% during a follow-up period of 72 h which was associated with a decrease in diuresis and natriuresis to 36 and 31%, respectively. Simultaneously, plasma renin concentration increased 30-fold indicating marked reduction of renal perfusion, while plasma renin substrate concentration fell to 6% of the baseline level. There was microscopic evidence of oligemic circulatory renal damage characterized by acute proximal tubular necrosis with concomitant tubular dilatation. Short-term infusion of homologous renin substrate-enriched plasma, derived from nephrectomized animals, was followed by marked increase in mean arterial blood pressure from 34 +/- 9 to 77 +/- 7 mm Hg accompanied by marked diuresis and natriuresis. Renin substrate depletion following galactosamine-induced fulminant liver failure may represent impaired hepatic biosynthesis as well as increased renin substrate consumption due to excessive renin secretion. Angiotensinogen repletion has a beneficial effect on both renal function and blood pressure probably due to marked generation of the potent vasoconstrictor angiotensin II which consequently inhibits renin secretion. These observations strongly support the suggestion that the renin-angiotensin system is of major importance to cardiovascular homeostasis in acute liver failure.

Topics: Angiotensinogen; Animals; Blood Pressure; Chemical and Drug Induced Liver Injury; Galactosamine; Guinea Pigs; Homeostasis; Kidney; Liver Diseases; Male; Renin; Renin-Angiotensin System

Ten patients with hepatorenal syndrome were evaluated before and after creation of a side-to-side portacaval shunt or insertion of a peritoneovenous shunt, procedures which produced an increase in plasma volume and cardiac output. In the seven patients who survived surgery, renal function improved significantly, plasma renin activity fell from high to normal levels, and low levels of plasma renin substrate increased. Prior to surgery, blockade of angiotension II by saralasin produced hypotension and an increase in plasma renin activity, whereas after surgery, saralasin had no effect on blood pressure or renin. Our findings suggest that decreased "effective" plasma volume may be important in the stimulation of renin release and possibly in the pathophysiology of renal failure in the hepatorenal syndrome.

Topics: Angiotensinogen; Blood Pressure; Creatinine; Female; Hemodynamics; Humans; Kidney Diseases; Liver Diseases; Male; Middle Aged; Plasma Volume; Portacaval Shunt, Surgical; Renin; Saralasin

Topics: Acute Kidney Injury; Aldosterone; Angiotensin II; Angiotensinogen; Ascites; Blood Pressure; Endopeptidases; Humans; Liver Diseases; Renin

Topics: Aldosterone; Angiotensin II; Angiotensinogen; Corticosterone; Hepatic Encephalopathy; Hepatitis; Humans; Hydrocortisone; Hyperaldosteronism; Liver Cirrhosis; Liver Diseases; Renin

Topics: Acute Kidney Injury; Angiotensin II; Angiotensinogen; Humans; Liver Diseases; Renin