GATA4, a new regulator of cardiac fibroblasts, is sensitive to natriuretic peptides

Abstract

Cardiac fibroblasts are the most prevalent cell type in the heart. These cells exert a critical role in regulating normal myocardial function and in adverse myocardial remodelling that occur with hypertension, myocardial infarction, and heart failure.1 In normal cardiac tissue, fibroblasts are found throughout the cardiac tissue in parallel to the prevailing direction of muscle fibres. In essence, every cardiac myocyte is therefore in direct contact with fibroblasts. Adverse myocardial remodelling includes enlargement of myocytes, proliferation of fibroblasts, and increased procollagen synthesis. Natriuretic peptides, including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), released from myocytes have been shown to act as autocine/paracrine factors that reduce myocyte hypertrophy and exert antifibrotic and antiproliferative effects on cardiac fibroblasts.2,3 Antifibrotic effects are attributed to C-type natriuretic peptide (CNP) released from endothelial cells and cardiac fibroblasts.4 Natriuretic peptides initiate their signalling via guanylyl cyclase receptors (NPR-A, NPR-B) and C-type receptor (NPR-C) all expressed in cardiac fibroblasts.3,4 These effects may be of particular importance during pathological conditions, when the fibrosis and increased deposition of collagen results in increased myocardial stiffness and diastolic dysfunction. Myocardial hypertrophy is also characterized by activation of transcription factors. A number of stimuli that induce myocyte hypertrophy are known to enhance GATA4 transcriptional activity through … *Corresponding author. Tel: +1 514 890 8000; fax: +1 514 412 7204; E-mail address : marek.jankowski{at}umontreal.ca