Review Article | Published:

Targeting BMP signalling in cardiovascular disease and anaemia

Nature Reviews Cardiology volume 13, pages 106120 (2016) | Download Citation

Abstract

Bone morphogenetic proteins (BMPs) and their receptors, known to be essential regulators of embryonic patterning and organogenesis, are also critical for the regulation of cardiovascular structure and function. In addition to their contributions to syndromic disorders including heart and vascular development, BMP signalling is increasingly recognized for its influence on endocrine-like functions in postnatal cardiovascular and metabolic homeostasis. In this Review, we discuss several critical and novel aspects of BMP signalling in cardiovascular health and disease, which highlight the cell-specific and context-specific nature of BMP signalling. Based on advancing knowledge of the physiological roles and regulation of BMP signalling, we indicate opportunities for therapeutic intervention in a range of cardiovascular conditions including atherosclerosis and pulmonary arterial hypertension, as well as for anaemia of inflammation. Depending on the context and the repertoire of ligands and receptors involved in specific disease processes, the selective inhibition or enhancement of signalling via particular BMP ligands (such as in atherosclerosis and pulmonary arterial hypertension, respectively) might be beneficial. The development of selective small molecule antagonists of BMP receptors, and the identification of ligands selective for BMP receptor complexes expressed in the vasculature provide the most immediate opportunities for new therapies.

Key points

  • Bone morphogenetic proteins (BMPs) have important roles in cardiovascular growth, homeostasis, and disease development

  • The wide repertoire of BMP ligands and receptors, coupled with numerous modifiers of BMP signalling, confer marked tissue-specific and cell-specific responses to BMPs

  • Understanding the context-specific nature of BMP signalling can help to guide the development of novel therapeutics to treat cardiovascular disease and anaemia

  • Small molecule inhibition of BMP signalling is efficacious in preclinical models of atherosclerosis, vascular calcification, and anaemia

  • Enhancement of BMP receptor-II (BMPR-II) signalling by increasing cell-surface levels of BMPR-II or by endothelial-selective BMPR-II agonists such as BMP9 shows promise in preclinical models of pulmonary arterial hypertension

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Affiliations

  1. Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK.

    • Nicholas W. Morrell
  2. Center for Immunology and Inflammatory Diseases, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Charlestown, MA 02129, USA.

    • Donald B. Bloch
  3. Department of Molecular Cell Biology and Cancer Genomics Centre Netherlands, Leiden University Medicine Centre, Albinusdreef 2, 2333 ZA Leiden, Netherlands.

    • Peter ten Dijke
    •  & Marie-Jose T. H. Goumans
  4. Cardiovascular Research Institute, University of California, 500 Parnassus Avenue, San Francisco, CA 94143, USA.

    • Akiko Hata
  5. MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.

    • Jim Smith
  6. Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.

    • Paul B. Yu
  7. Anaesthesia Centre for Critical Care Research, Department of Anaesthesia, Critical Care and Pain Medicine, 55 Fruit Street, Boston, MA 02114, USA.

    • Kenneth D. Bloch

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All the authors researched data for the article, discussed its content, wrote the manuscript, and reviewed/edited it before submission.

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Correspondence to Nicholas W. Morrell.

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https://doi.org/10.1038/nrcardio.2015.156

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