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GLP‐1 Is a Coronary Artery Vasodilator in Humans
BACKGROUND: The mechanism underlying the beneficial cardiovascular effects of the incretin GLP‐1 (glucagon‐like peptide 1) and its analogues in humans is elusive. We hypothesized that activating receptors located on vascular smooth muscle cells to induce either peripheral or coronary vasodilatation...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404441/ https://www.ncbi.nlm.nih.gov/pubmed/30571482 http://dx.doi.org/10.1161/JAHA.118.010321 |
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author | Clarke, Sophie J. Giblett, Joel P. Yang, Lucy L. Hubsch, Annette Zhao, Tian Aetesam‐ur‐Rahman, Muhammad West, Nick E. J. O'Sullivan, Michael Figg, Nichola Bennett, Martin Wewer Albrechtsen, Nicolai J. Deacon, Carolyn F. Cheriyan, Joseph Hoole, Stephen P. |
author_facet | Clarke, Sophie J. Giblett, Joel P. Yang, Lucy L. Hubsch, Annette Zhao, Tian Aetesam‐ur‐Rahman, Muhammad West, Nick E. J. O'Sullivan, Michael Figg, Nichola Bennett, Martin Wewer Albrechtsen, Nicolai J. Deacon, Carolyn F. Cheriyan, Joseph Hoole, Stephen P. |
author_sort | Clarke, Sophie J. |
collection | PubMed |
description | BACKGROUND: The mechanism underlying the beneficial cardiovascular effects of the incretin GLP‐1 (glucagon‐like peptide 1) and its analogues in humans is elusive. We hypothesized that activating receptors located on vascular smooth muscle cells to induce either peripheral or coronary vasodilatation mediates the cardiovascular effect of GLP‐1. METHODS AND RESULTS: Ten stable patients with angina awaiting left anterior descending artery stenting underwent forearm blood flow measurement using forearm plethysmography and post–percutaneous coronary intervention coronary blood flow measurement using a pressure‐flow wire before and after peripheral GLP‐1 administration. Coronary sinus and artery bloods were sampled for GLP‐1 levels. A further 11 control patients received saline rather than GLP‐1 in the coronary blood flow protocol. GLP‐1 receptor (GLP‐1R) expression was assessed by immunohistochemistry using a specific GLP‐1R monoclonal antibody in human tissue to inform the physiological studies. There was no effect of GLP‐1 on absolute forearm blood flow or forearm blood flow ratio after GLP‐1, systemic hemodynamics were not affected, and no binding of GLP‐1R monoclonal antibody was detected in vascular tissue. GLP‐1 reduced resting coronary transit time (mean [SD], 0.87 [0.39] versus 0.63 [0.27] seconds; P=0.02) and basal microcirculatory resistance (mean [SD], 76.3 [37.9] versus 55.4 [30.4] mm Hg/s; P=0.02), whereas in controls, there was an increase in transit time (mean [SD], 0.48 [0.24] versus 0.83 [0.41] seconds; P<0.001) and basal microcirculatory resistance (mean [SD], 45.9 [34.7] versus 66.7 [37.2] mm Hg/s; P=0.02). GLP‐1R monoclonal antibody binding was confirmed in ventricular tissue but not in vascular tissue, and transmyocardial GLP‐1 extraction was observed. CONCLUSIONS: GLP‐1 causes coronary microvascular dilation and increased flow but does not influence peripheral tone. GLP‐1R immunohistochemistry suggests that GLP‐1 coronary vasodilatation is indirectly mediated by ventricular‐coronary cross talk. |
format | Online Article Text |
id | pubmed-6404441 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-64044412019-03-18 GLP‐1 Is a Coronary Artery Vasodilator in Humans Clarke, Sophie J. Giblett, Joel P. Yang, Lucy L. Hubsch, Annette Zhao, Tian Aetesam‐ur‐Rahman, Muhammad West, Nick E. J. O'Sullivan, Michael Figg, Nichola Bennett, Martin Wewer Albrechtsen, Nicolai J. Deacon, Carolyn F. Cheriyan, Joseph Hoole, Stephen P. J Am Heart Assoc Original Research BACKGROUND: The mechanism underlying the beneficial cardiovascular effects of the incretin GLP‐1 (glucagon‐like peptide 1) and its analogues in humans is elusive. We hypothesized that activating receptors located on vascular smooth muscle cells to induce either peripheral or coronary vasodilatation mediates the cardiovascular effect of GLP‐1. METHODS AND RESULTS: Ten stable patients with angina awaiting left anterior descending artery stenting underwent forearm blood flow measurement using forearm plethysmography and post–percutaneous coronary intervention coronary blood flow measurement using a pressure‐flow wire before and after peripheral GLP‐1 administration. Coronary sinus and artery bloods were sampled for GLP‐1 levels. A further 11 control patients received saline rather than GLP‐1 in the coronary blood flow protocol. GLP‐1 receptor (GLP‐1R) expression was assessed by immunohistochemistry using a specific GLP‐1R monoclonal antibody in human tissue to inform the physiological studies. There was no effect of GLP‐1 on absolute forearm blood flow or forearm blood flow ratio after GLP‐1, systemic hemodynamics were not affected, and no binding of GLP‐1R monoclonal antibody was detected in vascular tissue. GLP‐1 reduced resting coronary transit time (mean [SD], 0.87 [0.39] versus 0.63 [0.27] seconds; P=0.02) and basal microcirculatory resistance (mean [SD], 76.3 [37.9] versus 55.4 [30.4] mm Hg/s; P=0.02), whereas in controls, there was an increase in transit time (mean [SD], 0.48 [0.24] versus 0.83 [0.41] seconds; P<0.001) and basal microcirculatory resistance (mean [SD], 45.9 [34.7] versus 66.7 [37.2] mm Hg/s; P=0.02). GLP‐1R monoclonal antibody binding was confirmed in ventricular tissue but not in vascular tissue, and transmyocardial GLP‐1 extraction was observed. CONCLUSIONS: GLP‐1 causes coronary microvascular dilation and increased flow but does not influence peripheral tone. GLP‐1R immunohistochemistry suggests that GLP‐1 coronary vasodilatation is indirectly mediated by ventricular‐coronary cross talk. John Wiley and Sons Inc. 2018-11-13 /pmc/articles/PMC6404441/ /pubmed/30571482 http://dx.doi.org/10.1161/JAHA.118.010321 Text en © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Original Research Clarke, Sophie J. Giblett, Joel P. Yang, Lucy L. Hubsch, Annette Zhao, Tian Aetesam‐ur‐Rahman, Muhammad West, Nick E. J. O'Sullivan, Michael Figg, Nichola Bennett, Martin Wewer Albrechtsen, Nicolai J. Deacon, Carolyn F. Cheriyan, Joseph Hoole, Stephen P. GLP‐1 Is a Coronary Artery Vasodilator in Humans |
title | GLP‐1 Is a Coronary Artery Vasodilator in Humans |
title_full | GLP‐1 Is a Coronary Artery Vasodilator in Humans |
title_fullStr | GLP‐1 Is a Coronary Artery Vasodilator in Humans |
title_full_unstemmed | GLP‐1 Is a Coronary Artery Vasodilator in Humans |
title_short | GLP‐1 Is a Coronary Artery Vasodilator in Humans |
title_sort | glp‐1 is a coronary artery vasodilator in humans |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404441/ https://www.ncbi.nlm.nih.gov/pubmed/30571482 http://dx.doi.org/10.1161/JAHA.118.010321 |
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