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Cardiovascular effects of relaxin: from basic science to clinical therapy

Nature Reviews Cardiology volume 7, pages 48–58 (2010)Cite this article

Abstract

Although substantial advances have been achieved in recent decades in the clinical management of heart diseases, new therapies that provide better or additional efficacy with minimal adverse effects are urgently required. Evidence that has accumulated since the 1990s indicates that the peptide hormone relaxin has multiple beneficial actions in the cardiovascular system under pathological conditions and, therefore, holds promise as a novel therapeutic intervention. Clinical trials for heart failure therapy using relaxin revealed several beneficial actions. Here we review findings from mechanistic and applied research in this field, comment on the outcomes of recent phase I/II clinical trails on patients with heart failure, and highlight settings of cardiovascular diseases where relaxin might be effective.

Key Points

  • Relaxin is a naturally occurring peptide hormone with a broad array of cardiovascular actions demonstrated in experimental models

  • Cardiovascular tissues are equipped with relaxin receptors that are activated by circulating relaxin or regionally generated relaxin and mediate a range of bioactivities via diverse signaling pathways

  • Experimental research has documented multiple cardioprotective actions of relaxin against key disease components, including myocardial injury, vasoconstriction, oxidative stress, fibrosis and inflammation

  • Clinical trials have also documented vasodilatory action of relaxin in patients with acute heart failure

  • Clinical trials have demonstrated that relaxin has a good safety profile when administered either intravenously or subcutaneously over a short or long period

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Figure 1: Signaling pathways activated by the relaxin receptor RXFP1.
Figure 2: A summary of the cardiac protective actions of relaxin based on experimental studies in a variety of animal models.

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Acknowledgements

This work was supported by National Health and Medical Research Council (NHMRC) of Australia Research Fellowships to X.-J. Du, A. M. Dart and R. A. D. Bathgate; a National Heart Foundation of Australia (NHFA)/NHMRC RD Wright Fellowship to C. S. Samuel; a NHMRC project grant 436,713 to R. J. Summers and R. A. D. Bathgate; a NHMRC program grant 519,461 to P. M. Sexton, A. Christopoulos and R. J. Summers; and a NHMRC program grant A72600 to A. M. Dart.

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Authors and Affiliations

  1. Experimental Cardiology Laboratory, Baker IDI Heart and Diabetes Institute, St. Kilda Road Central, Melbourne, 3008, Vic, Australia

    Xiao-Jun Du

  2. Florey Neurosciences Institute and Department of Biochemistry and Molecular Biology, University of Melbourne, Melbourne, Vic, Australia

    Ross A. D. Bathgate & Chrishan S. Samuel

  3. Alfred Heart Center, the Alfred Hospital and Central Medical School, Monash University, Melbourne, Vic, Australia

    Anthony M. Dart

  4. Monash Institute of Pharmaceutical Sciences & Department of Pharmacology, Drug Discovery Biology, Monash University, Melbourne, Vic, Australia

    Roger J. Summers

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  1. Xiao-Jun Du
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  2. Ross A. D. Bathgate
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Correspondence to Xiao-Jun Du.

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Du, XJ., Bathgate, R., Samuel, C. et al. Cardiovascular effects of relaxin: from basic science to clinical therapy. Nat Rev Cardiol 7, 48–58 (2010). https://doi.org/10.1038/nrcardio.2009.198

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