title: Molecular mechanisms underlying cardiac antihypertrophic and antifibrotic effects of natriuretic peptides.
abstract: Natriuretic peptides (NPs) exert well-characterized protective effects on the cardiovascular system, such as vasorelaxation, natri- and diuresis, increase of endothelial permeability, and inhibition of renin-angiotensin-aldosterone system. It has been reported that they also possess antihypertrophic and antifibrotic properties and contribute actively to cardiac remodeling. As a consequence, they are involved in several aspects of cardiovascular diseases. Antihypertrophic and antifibrotic actions of NPs appear to be mediated by specific signaling pathways within a more complex cellular network. Elucidation of the molecular mechanisms underlying the effects of NPs on cardiac remodeling represents an important research objective in order to gain more insights on the complex network leading to cardiac hypertrophy, ventricular dysfunction, and transition to heart failure, and in the attempt to develop novel therapeutic agents. The aim of the present article is to review well-characterized molecular mechanisms underlying the antihypertrophic and antifibrotic effects of NPs in the heart that appear to be mainly mediated by guanylyl cyclase type A receptor. In particular, we discuss the calcineurin/NFAT, the sodium exchanger NHE-1, and the TGFβ1/Smad signaling pathways. The role of guanylyl cyclase type B receptor, along with the emerging functional significance of natriuretic peptide receptor type C as mediators of CNP antihypertrophic and antifibrotic actions in the heart are also considered.
authors.affiliation: Cardiology, Department of Clinical and Molecular Medicine, School of Medicine and Psychology, University Sapienza of Rome, Ospedale S. Andrea, Rome, Italy.
authors.forename: Camilla
authors.initials: C
authors.lastname: Calvieri
authors.forename: Speranza
authors.initials: S
authors.lastname: Rubattu
authors.forename: Massimo
authors.initials: M
authors.lastname: Volpe
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism*; D005355:Fibrosis; D006801:Humans; D009206:Myocardium / Q000473:pathology*; D050778:NFATC Transcription Factors / Q000378:metabolism; D020098:Natriuretic Peptide, C-Type / Q000378:metabolism; D045265:Natriuretic Peptides / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D050778:NFATC Transcription Factors; D045265:Natriuretic Peptides; D051785:Smad Proteins; D017923:Sodium-Hydrogen Exchangers; D053773:Transforming Growth Factor beta1; C069139:growth factor-activatable Na-H exchanger NHE-1; D020098:Natriuretic Peptide, C-Type; D019703:Calcineurin