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      The role of tetrahydrobiopterin in inflammation and cardiovascular disease

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          Summary

          The cofactor tetrahydrobiopterin (BH4) is required for nitric oxide (NO) production by all nitric oxide synthase (NOS) enzymes and is a key regulator of cellular redox signalling. When BH4 levels become limiting NOS enzymes become ‘uncoupled’ and produce superoxide rather than NO. Endothelial cell BH4 is required for the maintenance of vascular function through NO production, and reduced BH4 levels are associated with vascular dysfunction. Evidence increasingly points to important roles for BH4 and NOS enzymes in other vascular cell types. Leukocytes have a fundamental role in atherosclerosis, and new evidence points to a role in the control of hypertension. Leukocytes are a major site of iNOS expression, and the regulation of this isoform is another mechanism by which BH4 availability may modulate disease. This review provides an overview of BH4 control of NOS function in both endothelial cells and leukocytes in the context of vascular disease and current therapeutic evaluations.

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          Author and article information

          Journal
          7608063
          7724
          Thromb Haemost
          Thromb. Haemost.
          Thrombosis and haemostasis
          0340-6245
          25 July 2016
          10 October 2012
          November 2012
          16 January 2017
          : 108
          : 5
          : 832-839
          Affiliations
          [1 ]Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK
          [2 ]Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
          Author notes
          Correspondence to: Prof. Keith Channon, Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Level 6 West Wing, Headley Way, Oxford, OX3 9DU, UK, Tel.: +44 1865572783, Fax: +44 1865287586, Keith.Channon@ 123456cardiov.ox.ac.uk
          Article
          PMC5238931 PMC5238931 5238931 ems63910
          10.1160/TH12-06-0424
          5238931
          23052970
          952389a7-9def-4c68-b340-4320902aaf6c

          For personal or educational use only. No other uses without permission. All rights reserved.

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          Categories
          Article

          reactive oxygen species (ROS),nitric oxide,vascular disease,BH4,Tetrahydrobiopterin

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