title: Expression of vasoactive proteins in gastric antral mucosa reflects vascular dysfunction in patients with cirrhosis and portal hypertension.
abstract: OBJECTIVE
  Patients with cirrhosis display hypocontractility of splanchnic vessels because of dysregulation of vasoactive proteins, such as decreased effect of RhoA/ROCK and increased activity of β-Arrestin-2 and eNOS. However, it is unknown whether the dysregulation of vasoactive proteins is displayed in other vessels. We investigated whether expression of vasoactive proteins can be evaluated in gastric mucosa vessels.
  
  
  METHODS
  Biopsies from the gastric mucosa of 111 patients with cirrhosis were collected at three different centres and from 13 controls. Forty-nine patients had received TIPS. Portal pressure gradient was measured in 49 patients with TIPS and in 16 patients without TIPS. Biopsies from the antrum were conserved in formaldehyde for immunohistochemistry or shock-frozen for PCR and Western blot.
  
  
  RESULTS
  The mucosal transcription of vascular markers (αSMA, CD31) was higher in cirrhotic patients than controls, which was confirmed by immunohistochemistry. On average, relative mucosal levels of RhoA and ROCK were lower, while β-Arrestin-2 levels were higher in cirrhotic patients compared to controls. Transcriptional levels of eNOS increased with presence of ascites and grade of oesophageal varices. Patients with TIPS showed less pronounced markers of vascular dysfunction in gastric mucosa.
  
  
  CONCLUSIONS
  This is the first evidence that the expression of vasoactive proteins in mucosa from the gastric antrum of patients with cirrhosis reflects their vascular dysfunction and possibly changes after therapeutic interventions.
authors.affiliation: Department of Internal Medicine I, University of Bonn, Bonn, Germany; Gastrounit, Medical Division, Hvidovre Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jonel
authors.initials: J
authors.lastname: Trebicka
authors.forename: Cyrus
authors.initials: C
authors.lastname: Wix
authors.forename: Matthias
authors.initials: M
authors.lastname: von Heydebrand
authors.forename: Kanishka
authors.initials: K
authors.lastname: Hittatiya
authors.forename: Thomas
authors.initials: T
authors.lastname: Reiberger
authors.forename: Sabine
authors.initials: S
authors.lastname: Klein
authors.forename: Robert
authors.initials: R
authors.lastname: Schierwagen
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.forename: Markus
authors.initials: M
authors.lastname: Peck-Radosavljevic
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Fischer
authors.forename: Søren
authors.initials: S
authors.lastname: Møller
authors.forename: Flemming
authors.initials: F
authors.lastname: Bendtsen
authors.forename: Aleksander
authors.initials: A
authors.lastname: Krag
authors.forename: Tilman
authors.initials: T
authors.lastname: Sauerbruch
mesh_terms: D000328:Adult; D000368:Aged; D019390:Arrestins / Q000032:analysis* / Q000235:genetics; D001706:Biopsy; D015153:Blotting, Western; D016022:Case-Control Studies; D003718:Denmark; D005260:Female; D005753:Gastric Mucosa / Q000737:chemistry*; D006801:Humans; D006975:Hypertension, Portal / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery; D007150:Immunohistochemistry; D008103:Liver Cirrhosis / Q000150:complications* / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000032:analysis* / Q000235:genetics; D016133:Polymerase Chain Reaction; D017082:Portal Pressure; D019168:Portasystemic Shunt, Transjugular Intrahepatic; D011706:Pyloric Antrum / Q000737:chemistry*; D012333:RNA, Messenger / Q000032:analysis; D013152:Splanchnic Circulation; D055815:Young Adult; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D054460:rho-Associated Kinases / Q000032:analysis* / Q000235:genetics; D020742:rhoA GTP-Binding Protein / Q000032:analysis* / Q000235:genetics
chemical_list: C000605254:ARRB2 protein, human; D019390:Arrestins; D012333:RNA, Messenger; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; C066737:RHOA protein, human; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein
keywords: cirrhosis; portal hypertension; transjugular intrahepatic portosystemic shunt; vascular dysfunction; vasoactive pathways