Neutral endopeptidase is activated in cardiomyocytes in human aortic valve stenosis and heart failure

Article

关键词: ANGIOTENSIN-CONVERTING ENZYME;    BRADYKININ;    CARDIOMYOPATHY;    ENKEPHALINASE;    DEGRADATION;    HYPERTROPHY;    RAT;   

DOI  :  10.1161/hc0302.103593

来源: SCIE

【 摘 要 】

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.

【 授权许可】

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