Title: Induction of Myocardial Fibrosis and Hypertrophy by Natriuretic Peptides
Volume: 1
Issue: 3
Author(s): Paul J. Lijnen, Victor V. Petrov and Robert H. Fagard
Affiliation:
Keywords:
natriuretic peptides, cardiac hypertrophy, myocardial fibrosis, infarction, heart failure, neutral endopeptidase inhibition
Abstract: The heart is a major site of natriuretic peptides (NP). Atrial and brain natriuretic peptide (ANP and BNP) are predominantly produced by atria and ventricles. C-Natriuretic peptide (CNP) is also found in heart tissue. ANP and BNP are produced by cardiomyocytes and fibroblasts. Cardiac fibroblasts also secrete CNP. Three NP-receptors (NPR-A, NPRB, NPR-C) are expressed in heart atria and ventricles. ANP, BNP and CNP exert antihypertrophic actions in cardiomyocytes, suppress cardiac fibroblast growth and inhibit collagen synthesis in cardiac fibroblasts. In vivo infusion of ANP also reduces collagen deposition in the arterial wall of spontaneously hypertensive rats. Baseline plasma BNP is a sensitive predictor of morbidity and mortality in heart failure and changes in BNP over time are associated with corresponding changes in subsequent mortality and morbidity. Plasma BNP, and to a lesser extent ANP, is also a strong cardiovascular risk marker in patients with essential hypertension and left ventricular hypertrophy without left ventricle dysfunction or overt renal disease. A potential role for genetic variants of the ANP gene in the modulation of the disease phenotype observed with some cardiovascular diseases is also reported. Neutral endopeptidase inhibition may also have inhibitory effects on cardiac hypertrophy and fibrosis.
