title: Abnormal plasma microparticles impair vasoconstrictor responses in patients with cirrhosis.
abstract: OBJECTIVE
  Circulating membrane-shed microparticles (MPs) participate in regulation of vascular tone. We investigated the cellular origins of MPs in plasma from patients with cirrhosis and assessed the contribution of MPs to arterial vasodilation, a mechanism that contributes to portal hypertension.
  
  
  METHODS
  We analyzed MPs from blood samples of 91 patients with cirrhosis and 30 healthy individuals (controls) using flow cytometry; their effects on the vascular response to vasoconstrictors were examined in vitro and in vivo.
  
  
  RESULTS
  Circulating levels of leuko-endothelial (CD31(+)/41(-)), pan-leukocyte (CD11a(+)), lymphocyte (CD4(+)), and erythrocyte (CD235a(+)) MPs were higher in patients with cirrhosis than in controls. Plasma of patients with cirrhosis contained hepatocyte-derived MPs (cytokeratin-18(+)), whereas plasma from controls did not. The severity of cirrhosis and systemic inflammation were major determinants of the levels of leuko-endothelial and hepatocyte MPs. MPs from patients with advanced cirrhosis significantly impaired contraction of vessels in response to phenylephrine, whereas MPs from healthy controls or from patients of Child-Pugh class A did not. This effect depended on cyclooxygenase type 1 and required phosphatidylserine on the surface of MPs. Intravenous injection of MPs from patients with cirrhosis into BALB/C mice decreased mean arterial blood pressure.
  
  
  CONCLUSIONS
  Cirrhosis is associated with increases in circulating subpopulations of MPs, likely resulting from systemic inflammation and liver cell damage. The overall pool of circulating MPs from patients with advanced cirrhosis impairs vasoconstrictor responses and decreases blood pressure, contributing to the arterial vasodilation associated with portal hypertension.
authors.affiliation: INSERM Unité 970, Paris Cardiovascular Research Center - PARCC, Paris, France.
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Rautou
authors.forename: Julie
authors.initials: J
authors.lastname: Bresson
authors.forename: Yannis
authors.initials: Y
authors.lastname: Sainte-Marie
authors.forename: Anne-Clemence
authors.initials: AC
authors.lastname: Vion
authors.forename: Valerie
authors.initials: V
authors.lastname: Paradis
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Renard
authors.forename: Cecile
authors.initials: C
authors.lastname: Devue
authors.forename: Christophe
authors.initials: C
authors.lastname: Heymes
authors.forename: Philippe
authors.initials: P
authors.lastname: Letteron
authors.forename: Laure
authors.initials: L
authors.lastname: Elkrief
authors.forename: Didier
authors.initials: D
authors.lastname: Lebrec
authors.forename: Dominique
authors.initials: D
authors.lastname: Valla
authors.forename: Alain
authors.initials: A
authors.lastname: Tedgui
authors.forename: Richard
authors.initials: R
authors.lastname: Moreau
authors.forename: Chantal M
authors.initials: CM
authors.lastname: Boulanger
mesh_terms: D000328:Adult; D055252:Cell-Derived Microparticles; D004108:Dilatation, Pathologic / Q000503:physiopathology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006975:Hypertension, Portal / Q000503:physiopathology*; D008103:Liver Cirrhosis / Q000097:blood / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
chemical_list: D014662:Vasoconstrictor Agents