title: Increased expression of the renin-angiotensin system and mast cell density but not of angiotensin-converting enzyme II in late stages of human heart failure.
abstract: BACKGROUND
  The activation of the renin-angiotensin system (RAS) contributes to the progression of left ventricular dysfunction. A novel human homologue of the angiotensin-converting enzyme (ACE), named ACE2, has been described but its role in human heart failure (HF) has not been elucidated. Besides, there is controversy as to whether the major angiotensin II-forming-activity in heart is ACE or chymase released from mast cells. Furthermore, long-term blockade of nitric oxide (NO) synthesis has been shown to increase ACE activity. To assess the locally activated vasoactive mediators that may contribute to the ventricular deterioration process, we sought to simultaneously analyze their expression in failing hearts.
  
  
  METHODS
  We analyzed left ventricular biopsies from 30 patients with heart failure undergoing heart transplantation and 12 organ donors. The mRNA levels of ACE, ACE2, chymase and endothelial nitric oxide synthase (eNOS), were quantified by real-time polymerase chain reaction and mast cell density was assessed by immunohistochemistry. The mRNA levels of the atrial natriuretic peptide (ANP) and the brain natriuretic peptide (BNP) were also quantified as controls.
  
  
  RESULTS
  There was higher ACE and chymase mRNA expression and mast cell density in failing than in control myocardium and no changes in ACE2 expression were detected. eNOS mRNA levels were lower in failing hearts. Both ANP and BNP expression were higher in pathological than in control samples.
  
  
  CONCLUSIONS
  These data document a decompensation of vasoactive systems that may contribute to the progressive impairment of the myocardial function in HF. On the other hand, ACE2 mRNA expression is not altered in human end-stage HF.
authors.affiliation: Experimental Cardiology Laboratory, Hospital Clínic de Barcelona and Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain. mbatlle@clinic.ub.es
authors.forename: Montserrat
authors.initials: M
authors.lastname: Batlle
authors.forename: Eulàlia
authors.initials: E
authors.lastname: Roig
authors.forename: Fèlix
authors.initials: F
authors.lastname: Perez-Villa
authors.forename: Sergio
authors.initials: S
authors.lastname: Lario
authors.forename: Pilar
authors.initials: P
authors.lastname: Cejudo-Martin
authors.forename: Ester
authors.initials: E
authors.lastname: García-Pras
authors.forename: José
authors.initials: J
authors.lastname: Ortiz
authors.forename: Mercé
authors.initials: M
authors.lastname: Roqué
authors.forename: Josefina
authors.initials: J
authors.lastname: Orús
authors.forename: Montserrat
authors.initials: M
authors.lastname: Rigol
authors.forename: Magdalena
authors.initials: M
authors.lastname: Heras
authors.forename: José
authors.initials: J
authors.lastname: Ramírez
authors.forename: Wladimiro
authors.initials: W
authors.lastname: Jimenez
mesh_terms: D000328:Adult; D000368:Aged; D000085962:Angiotensin-Converting Enzyme 2; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D001706:Biopsy; D002303:Cardiac Output, Low / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002452:Cell Count; D053818:Chymases; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000235:genetics / Q000502:physiology*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D012333:RNA, Messenger; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; D012697:Serine Endopeptidases; D053818:Chymases