Tetrahydrobiopterin restores impaired coronary microvascular dysfunction in hypercholesterolaemia
Open accessAbstract
Purpose Tetrahydrobiopterin (BH4) is an essential co-factor for the synthesis of nitric oxide (NO), and BH4 deficiency may cause impaired NO synthase (NOS) activity. We studied whether BH4 deficiency contributes to the coronary microcirculatory dysfunction observed in patients with hypercholesterolaemia.Methods Myocardial blood flow (MBF; ml min(-1) g(-1)) was measured at rest, during adenosine-induced (140 microg kg(-1) min(-1) over 7 min) hyperaemia (mainly non-endothelium dependent) and immediately after supine bicycle exercise (endothelium-dependent) stress in ten healthy volunteers and in nine hypercholesterolaemic subjects using 15O-labelled water and positron emission tomography. Measurements were repeated 60 min later, after intravenous infusion of BH4 (10 mg kg(-1) body weight over 30 min). Adenosine-induced hyperaemic MBF is considered to represent (near) maximal flow. Flow reserve utilisation was calculated as the ratio of exercise-induced to adenosine-induced hyperaemic MBF and expressed as percent to indicate how much of the maximal (adenosine-induced) hyperaemia can be achieved by bicycle stress.Results BH4 increased exercise-induced hyperaemia in controls (2.96+/-0.58 vs 3.41+/-0.73 ml min(-1) g(-1), p<0.05) and hypercholesterolaemic subjects (2.47+/-0.78 vs 2.70+/-0.72 ml min(-1) g(-1), p<0.01) but had no influence on MBF at rest or during adenosine-induced hyperaemia in controls (4.52+/-1.10 vs 4.85+/-0.45 ml min(-1) g(-1), p=NS) or hypercholesterolaemic subjects (4.86+/-1.18 vs 4.53+/-0.93 ml min(-1) g(-1), p=NS). Flow reserve utilisation remained unchanged in controls (70+/-17% vs 71+/-19%, p=NS) but increased significantly in hypercholesterolaemic subjects (53+/-15% vs 66+/-14%, p<0.05).Conclusion BH4 restores flow reserve utilisation of the coronary microcirculation in hypercholesterolaemic subjects, suggesting that BH4 deficiency may contribute to coronary microcirculatory dysfunction in hypercholesterolaemia.
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Studies assessing coronary artery function in patients with atherosclerosis did not find improvement after BH4 treatment.
“Studies, including the assessment of coronary artery function in patients with atherosclerosis, did not find an improvement after BH4 treatment (1028).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [1028]
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- Authors
- Wyss, C. A., Koepfli, P., Namdar, M., Siegrist, P. T., Luscher, T. F., Camici, P. G., & Kaufmann, P. A.
- Affiliations
- University Hospital Zurich (CH)
- Hammersmith Hospital (GB)
- Corresponding author
- Kaufmann, Philipp A
- Venue
- European Journal of Nuclear Medicine and Molecular Imaging
- Published
- 2004-07-31
- Volume
- 32
- Issue
- 1
- Pages
- 84-91
- ISSN
- 1619-7070 (ISSN-L)
- 1619-7089
- OpenAlex
- W2128888081
- Cited by
- 37
- References
- 38
- Citations by year
- 2021: 1 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 1 · 2012: 2
- FWCI
- 2.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- European Journal of Nuclear Medicine and Molecular Imaging (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- reroDoc Digital Library (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (68835)
- EMDO Stiftung
- Topics
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
- Health Sciences › Medicine › Surgery › Coronary Interventions and Diagnostics
- Keywords
- tetrahydrobiopterin, hypercholesterolemia, coronary microvascular dysfunction, nitric oxide synthase, nitric oxide, myocardial blood flow, flow reserve, 15O-water PET, coronary microcirculation, BH4 supplementation, endothelium-dependent vasodilation, endothelium-independent relaxation
- MeSH terms
- Adult, Antioxidants, Biopterins, Blood Flow Velocity, Exercise Test, Humans, Hypercholesterolemia, Infusions, Intravenous, Male, Microcirculation, Middle Aged, Radionuclide Imaging, Treatment Outcome, Recovery of Function
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