title: Neutral endopeptidase is activated in cardiomyocytes in human aortic valve stenosis and heart failure.
abstract: BACKGROUND
  The regulation of the cardiac neutral endopeptidase (EC 24.10, NEP) that degrades bradykinin and natriuretic peptides has been investigated in human cardiac hypertrophy and heart failure. Methods and Results- NEP mRNA was quantitated by real-time polymerase chain reaction (PCR) in left ventricular biopsies from patients with aortic valve stenosis (AS, n=19) and heart failure due to dilated cardiomyopathy (DCM, n=14), and control subjects with normal systolic function (CON, n=14). Left ventricular NEP mRNA content was increased 3-fold in AS (P<0.005) and 4.1-fold in DCM (P<0.002). The increase in NEP mRNA was related to the increase in end diastolic pressure in AS and DCM. In a second series, myocardial NEP enzymatic activity was determined. It increased 3.6-fold in AS (P<0.02) and 4-fold in DCM (P<0.002). NEP was localized in the myocardium by immunofluorescence microscopy and in situ PCR to myocytes and nonmyocyte areas and cells.
  
  
  CONCLUSIONS
  Elevated cardiac NEP activity in pressure loaded and failing human hearts may increase the local degradation of bradykinin and natriuretic peptides.
authors.affiliation: Klinik für Herz-, Gefäss- und Thoraxchirurgie, DHZB (R.P., H.R.Z., R.H., V.R.-Z.), Berlin, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Fielitz
authors.forename: Andreas
authors.initials: A
authors.lastname: Dendorfer
authors.forename: Reinhard
authors.initials: R
authors.lastname: Pregla
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ehler
authors.forename: Heinz R
authors.initials: HR
authors.lastname: Zurbrügg
authors.forename: Jozef
authors.initials: J
authors.lastname: Bartunek
authors.forename: Roland
authors.initials: R
authors.lastname: Hetzer
authors.forename: Vera
authors.initials: V
authors.lastname: Regitz-Zagrosek
mesh_terms: D001024:Aortic Valve Stenosis / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D004789:Enzyme Activation; D005455:Fluorescent Antibody Technique; D006333:Heart Failure / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D006352:Heart Ventricles / Q000201:enzymology; D006801:Humans; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000201:enzymology; D015260:Neprilysin / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D015533:Transcriptional Activation
chemical_list: D012333:RNA, Messenger; D015260:Neprilysin