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Molecular mechanisms underlying cardiac antihypertrophic and antifibrotic effects of natriuretic peptides

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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.

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Acknowledgments

The present work was supported by a grant (Ricerca Corrente) from the Italian Ministry of Health to MV and SR; by the 5‰ grant to MV and SR; and by the Ingenious HyperCare European project to MV.

Conflicts of interest

There are no conflicts of interest to disclose.

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Authors and Affiliations

  1. Cardiology, Department of Clinical and Molecular Medicine, School of Medicine and Psychology, University Sapienza of Rome, Ospedale S. Andrea, Rome, Italy

    Camilla Calvieri, Speranza Rubattu & Massimo Volpe

  2. IRCCS Neuromed, Pozzilli (Is), Italy

    Speranza Rubattu & Massimo Volpe

  3. Chair and Division of Cardiology, School of Medicine and Psychology, University Sapienza, Sant’Andrea Hospital, Via di Grottarossa, 1035-9, Rome, Italy

    Massimo Volpe

Authors
  1. Camilla Calvieri
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  2. Speranza Rubattu
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  3. Massimo Volpe
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Correspondence to Massimo Volpe.

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Calvieri, C., Rubattu, S. & Volpe, M. Molecular mechanisms underlying cardiac antihypertrophic and antifibrotic effects of natriuretic peptides. J Mol Med 90, 5–13 (2012). https://doi.org/10.1007/s00109-011-0801-z

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  • DOI: https://doi.org/10.1007/s00109-011-0801-z

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