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Atrial natriuretic peptide affects cardiac remodeling, function, heart failure, and survival in a mouse model of dilated cardiomyopathy.

ABSTRACT: Dilated cardiomyopathy is a frequent cause of heart failure and death. Atrial natriuretic peptide (ANP) is a biomarker of dilated cardiomyopathy, but there is controversy whether ANP modulates the development of heart failure. Therefore, we examined whether ANP affects heart failure, cardiac remodeling, function, and survival in a well-characterized, transgenic model of dilated cardiomyopathy. Mice with dilated cardiomyopathy with normal ANP levels survived longer than mice with partial ANP (P<0.01) or full ANP deficiency (P<0.001). In dilated cardiomyopathy mice, ANP protected against the development of heart failure as indicated by reduced lung water, alveolar congestion, pleural effusions, etc. ANP improved systolic function and reduced cardiomegaly. Pathological cardiac remodeling was diminished in mice with normal ANP as indicated by decreased ventricular interstitial and perivascular fibrosis. Mice with dilated cardiomyopathy and normal ANP levels had better systolic function (P<0.001) than mice with dilated cardiomyopathy and ANP deficiency. Dilated cardiomyopathy was associated with diminished cardiac transcripts for NP receptors A and B in mice with normal ANP and ANP deficiency, but transcripts for NP receptor C and C-type natriuretic peptide were selectively altered in mice with dilated cardiomyopathy and ANP deficiency. Taken together, these data indicate that ANP has potent effects in experimental dilated cardiomyopathy that reduce the development of heart failure, prevent pathological remodeling, preserve systolic function, and reduce mortality. Despite the apparent overlap in physiological function between the NPs, these data suggest that the role of ANP in dilated cardiomyopathy and heart failure is not compensated physiologically by other NPs.

SUBMITTER: Wang D

PROVIDER: S-EPMC4015109 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Atrial natriuretic peptide affects cardiac remodeling, function, heart failure, and survival in a mouse model of dilated cardiomyopathy.

Wang Dong D Gladysheva Inna P IP Fan Tai-Hwang M TH Sullivan Ryan R Houng Aiilyan K AK Reed Guy L GL

Hypertension (Dallas, Tex. : 1979) 20131230 3

Dilated cardiomyopathy is a frequent cause of heart failure and death. Atrial natriuretic peptide (ANP) is a biomarker of dilated cardiomyopathy, but there is controversy whether ANP modulates the development of heart failure. Therefore, we examined whether ANP affects heart failure, cardiac remodeling, function, and survival in a well-characterized, transgenic model of dilated cardiomyopathy. Mice with dilated cardiomyopathy with normal ANP levels survived longer than mice with partial ANP (P<0 ...[more]

PMID: 24379183

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Project description:AimsLeft atrial (LA) remodelling is an important predictor of cardiovascular events of heart failure (HF) and atrial fibrillation. Data regarding diagnostic value of LA remodelling on diastolic dysfunction (DD) and preclinical HF remain largely unexplored.Methods and resultsWe assessed LA dimension (LAD) in 8368 consecutive asymptomatic Asians (mean age: 49.7, 38.9% women) and related such measure to updated American Society of Echocardiography (ASE) DD criteria and newly revised N-terminal pro-brain natriuretic peptide (NT-proBNP) cut-off (≥125 pg/mL) and HF with preserved ejection fraction criteria incorporating NT-proBNP and echocardiography parameters by the European Society of Cardiology (ESC). LAD and indexed LAD (LADi) were both inversely correlated with myocardial relaxation e' and positively associated with indexed LA volume, left ventricular E/e', and tricuspid regurgitation velocity (all P < 0.001) and showed significantly graded increase across ASE-defined 'normal', 'inconclusive', and 'DD' categories (30.9, 34.4, and 36.5 mm; 16.7, 19.1, and 20.6 mm/m2 , for LAD/LADi, both P for trend: <0.001, respectively). Substantial differences of LAD/LADi (31.3 vs. 33.6 mm/16.7 vs. 19.2 mm/m2 , both P < 0.001) between ESC low and high HF probability using NT-proBNP cut-off were also observed. Multivariate linear and logistic models demonstrated that LAD set at 34 mm was independently associated with ASE-defined diastolic indices, DD existence, and elevated NT-proBNP (all P < 0.05). The use of LAD further yielded high diagnostic accuracy in DD (area under receiving operative characteristic curve: 0.77, 95% confidence interval [0.73, 0.80]; negative predictive value: 97.9%) and in ESC-recommended HF with preserved ejection fraction criteria (area under receiving operative characteristic curve: 0.70, 95% confidence interval [0.65, 0.75]; negative predictive value: 98.7%) with high predictive value in LA remodelling (>34 mL/m2 ; positive predictive value: 96%) and well-discriminated ESC-recommended NT-proBNP (≥125 pg/mL, LAD: 37 mm) for HF.ConclusionsSingle utilization of atrial remodelling is highly useful for ruling out presence of DD and provides practical threshold for identifying preclinical HF based on most updated guidelines.

Dataset Information

Atrial natriuretic peptide affects cardiac remodeling, function, heart failure, and survival in a mouse model of dilated cardiomyopathy.

Publications

Atrial natriuretic peptide affects cardiac remodeling, function, heart failure, and survival in a mouse model of dilated cardiomyopathy.

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