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Cardiac natriuretic peptides

Nature Reviews Cardiology volume 17, pages 698–717 (2020)Cite this article

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Abstract

Investigations into the mixed muscle–secretory phenotype of cardiomyocytes from the atrial appendages of the heart led to the discovery that these cells produce, in a regulated manner, two polypeptide hormones — the natriuretic peptides — referred to as atrial natriuretic factor or atrial natriuretic peptide (ANP) and brain or B-type natriuretic peptide (BNP), thereby demonstrating an endocrine function for the heart. Studies on the gene encoding ANP (NPPA) initiated the field of modern research into gene regulation in the cardiovascular system. Additionally, ANP and BNP were found to be the natural ligands for cell membrane-bound guanylyl cyclase receptors that mediate the effects of natriuretic peptides through the generation of intracellular cGMP, which interacts with specific enzymes and ion channels. Natriuretic peptides have many physiological actions and participate in numerous pathophysiological processes. Important clinical entities associated with natriuretic peptide research include heart failure, obesity and systemic hypertension. Plasma levels of natriuretic peptides have proven to be powerful diagnostic and prognostic biomarkers of heart disease. Development of pharmacological agents that are based on natriuretic peptides is an area of active research, with vast potential benefits for the treatment of cardiovascular disease.

Key points

  • The dual contractile–secretory phenotype of atrial (appendage) cardiomyocytes underlies the regulated secretion of two natriuretic peptide (NP) hormones: atrial NP and B-type NP.

  • Investigation into the genes encoding NPs has provided valuable insights into gene regulation in the cardiovascular system.

  • NPs are ligands for receptors that are membrane-bound guanylyl cyclases, thereby signalling through increases in intracellular levels of cGMP, which in turn interact with cGMP-dependent enzymes and ion channels in many cell types.

  • In addition to their roles in water and electrolyte balance, NPs participate in seemingly unrelated processes, such as immune response and lipid metabolism.

  • Plasma levels of NPs are useful clinical indicators in the diagnosis and prognosis of cardiovascular diseases.

  • NPs, their chemical derivatives and pharmacological agents that slow their catabolic rate are areas of active research that have produced useful new approaches in the treatment of systemic hypertension and heart failure.

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Fig. 1: Specific atrial granules.
Fig. 2: Expression and regulation of NPPA–NPPB.
Fig. 3: Natriuretic peptide processing and primary structure.
Fig. 4: Proposed intracellular transport and secretion of natriuretic peptides in cardiomyocytes.
Fig. 5: Morphological localization of atrial natriuretic peptide.
Fig. 6: Cognate receptors for natriuretic peptides.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Rigshospitalet University Hospital, Copenhagen, Denmark

    Jens P. Goetze

  2. Gladstone Institutes, San Francisco, CA, USA

    Benoit G. Bruneau

  3. Department of Pediatrics and Cardiovascular Research Institute, University of California, San Francisco, CA, USA

    Benoit G. Bruneau

  4. Division of Cardiology, Instituto Modelo de Cardiología, Córdoba, Argentina

    Hugo R. Ramos

  5. Department of Internal Medicine, Faculty of Medicine, National University of Córdoba, Córdoba, Argentina

    Hugo R. Ramos

  6. Department of Nutrition Management, Minami Kyushu University, Miyazaki, Japan

    Tsuneo Ogawa

  7. Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada

    Mercedes Kuroski de Bold & Adolfo J. de Bold

  8. University of Ottawa Heart Institute, Ottawa, ON, Canada

    Mercedes Kuroski de Bold & Adolfo J. de Bold

Authors
  1. Jens P. Goetze
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  2. Benoit G. Bruneau
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  3. Hugo R. Ramos
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  4. Tsuneo Ogawa
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  5. Mercedes Kuroski de Bold
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  6. Adolfo J. de Bold
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Contributions

J.P.G., B.G.B., H.R.R., T.O. and M.K.d.B. researched data for the article. All the authors discussed the content of the manuscript. J.P.G., B.G.B., H.R.R., M.K.d.B. and A.J.d.B. wrote the manuscript. All the authors reviewed and edited the manuscript before submission.

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Correspondence to Adolfo J. de Bold.

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Nature Reviews Cardiology thanks A. Clerico and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Goetze, J.P., Bruneau, B.G., Ramos, H.R. et al. Cardiac natriuretic peptides. Nat Rev Cardiol 17, 698–717 (2020). https://doi.org/10.1038/s41569-020-0381-0

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