Neutral endopeptidase is activated in cardiomyocytes in human aortic valve stenosis and heart failure.
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.
Fielitz
Jens
J
Klinik für Herz-, Gefäss- und Thoraxchirurgie, DHZB (R.P., H.R.Z., R.H., V.R.-Z.), Berlin, Germany.
Dendorfer
Andreas
A
Pregla
Reinhard
R
Ehler
Elisabeth
E
Zurbrügg
Heinz R
HR
Bartunek
Jozef
J
Hetzer
Roland
R
Regitz-Zagrosek
Vera
V
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
D012333:RNA, Messenger; D015260:Neprilysin