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Tetrahydrobiopterin: pleiotropic roles in cardiovascular pathophysiology
  1. Colin Cunnington,
  2. Keith M Channon
  1. Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
  1. Correspondence to Professor Keith M Channon, Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK; keith.channon{at}cardiov.ox.ac.uk

Abstract

Tetrahydrobiopterin (BH4) functions as a cofactor in several important enzyme systems. Substantial evidence implicates BH4 as a key regulator of endothelial nitric oxide synthase (eNOS) in the setting of endothelial dysfunction and atherosclerosis. Investigators have now taken early steps in addressing the potential of BH4 as a therapeutic strategy. However, it has become more apparent that the role of BH4 in other enzymatic pathways, including other NOS isoforms and the aromatic amino acid hydroxylases, may have a bearing on important aspects of cardiovascular homeostasis. Together with eNOS, these enzymes may play key roles in diverse cardiovascular disease states such as ischaemia-reperfusion injury, cardiac hypertrophy, cardiac autonomic function and pulmonary hypertension. This review provides an overview of the role of BH4 in cardiovascular pathophysiology.

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Footnotes

  • Funding Work in the authors' laboratory is supported by the British Heart Foundation (grants RG/07/003/23133 and PG/08/119/26263) and by the NIHR Oxford Biomedical Research Centre.

  • Competing interests The authors are investigators in the OXBIO study (NCT00423280) of oral BH4 treatment, supported by BioMarin Pharmaceutical Inc.

  • Provenance and peer review Commissioned; externally peer reviewed.

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