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.
BACKGROUND: The regulation of the cardiac neutral endopeptidase (EC 24.10, NEP) that degrades bradykinin and natriuretic peptides has been investigated in humancardiac 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: Alina Maloyan; James Gulick; Charles G Glabe; Rakez Kayed; Jeffrey Robbins Journal: Proc Natl Acad Sci U S A Date: 2007-03-26 Impact factor: 11.205
Authors: Aaron J Trask; Leanne Groban; Brian M Westwood; Jasmina Varagic; Detlev Ganten; Patricia E Gallagher; Mark C Chappell; Carlos M Ferrario Journal: Am J Hypertens Date: 2010-03-18 Impact factor: 2.689
Authors: Naveen L Pereira; Pinar Aksoy; Irene Moon; Yi Peng; Margaret M Redfield; John C Burnett; Eric D Wieben; Vivien C Yee; Richard M Weinshilboum Journal: J Mol Cell Cardiol Date: 2010-08-06 Impact factor: 5.000