doi: 10.1161/hc0302.103593
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(Circulation. 2002;105:286.)
© 2002 American Heart Association, Inc.
Brief Rapid Communications |
Neutral Endopeptidase Is Activated in Cardiomyocytes in Human Aortic Valve Stenosis and Heart Failure
From the Klinik für Herz-, Gefäß- und Thoraxchirurgie, DHZB (R.P., H.R.Z., R.H., V.R.-Z.), Berlin, Germany; Franz-Volhard-Klinik/Charite (J.F.), Berlin, Germany; Medical University Pharmacology and Toxicology (A.D.), Luebeck, Germany; Institut für Zellbiologie, ETH (E.E.), Zurich, Switzerland; and Cardiovascular Center (J.B.), Aalst, Belgium.
Correspondence to Vera Regitz-Zagrosek, DHZB, Augustenburger Platz 1, 13353 Berlin, Germany. E-mail zagrosek{at}dhzb.de
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.
Key Words: hypertrophy • cardiomyopathy • heart failure • metalloproteinases
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