GLP-1 Is a Coronary Artery Vasodilator in Humans

Research output: Contribution to journalJournal articleResearchpeer-review

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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; Albrechtsen, Nicolai J. Wewer; Deacon, Carolyn F.; Cheriyan, Joseph; Hoole, Stephen P.

In: Journal of the American Heart Association, Vol. 7, No. 22, e010321, 20.11.2018.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Clarke, SJ, Giblett, JP, Yang, LL, Hubsch, A, Zhao, T, Aetesam-ur-Rahman, M, West, NEJ, O'Sullivan, M, Figg, N, Bennett, M, Albrechtsen, NJW, Deacon, CF, Cheriyan, J & Hoole, SP 2018, 'GLP-1 Is a Coronary Artery Vasodilator in Humans', Journal of the American Heart Association, vol. 7, no. 22, e010321. https://doi.org/10.1161/JAHA.118.010321

APA

Clarke, S. J., Giblett, J. P., Yang, L. L., Hubsch, A., Zhao, T., Aetesam-ur-Rahman, M., ... Hoole, S. P. (2018). GLP-1 Is a Coronary Artery Vasodilator in Humans. Journal of the American Heart Association, 7(22), [e010321]. https://doi.org/10.1161/JAHA.118.010321

Vancouver

Clarke SJ, Giblett JP, Yang LL, Hubsch A, Zhao T, Aetesam-ur-Rahman M et al. GLP-1 Is a Coronary Artery Vasodilator in Humans. Journal of the American Heart Association. 2018 Nov 20;7(22). e010321. https://doi.org/10.1161/JAHA.118.010321

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 ; Albrechtsen, Nicolai J. Wewer ; Deacon, Carolyn F. ; Cheriyan, Joseph ; Hoole, Stephen P. / GLP-1 Is a Coronary Artery Vasodilator in Humans. In: Journal of the American Heart Association. 2018 ; Vol. 7, No. 22.

Bibtex

@article{3d28488f82e24f5186409ee03b2ca631,
title = "GLP-1 Is a Coronary Artery Vasodilator in Humans",
abstract = "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.",
keywords = "coronary blood flow reserve, coronary microvascular function, coronary microvascular resistance, GLP-1 (glucagon-like peptide 1)",
author = "Clarke, {Sophie J.} and Giblett, {Joel P.} and Yang, {Lucy L.} and Annette Hubsch and Tian Zhao and Muhammad Aetesam-ur-Rahman and West, {Nick E. J.} and Michael O'Sullivan and Nichola Figg and Martin Bennett and Albrechtsen, {Nicolai J. Wewer} and Deacon, {Carolyn F.} and Joseph Cheriyan and Hoole, {Stephen P.}",
year = "2018",
month = "11",
day = "20",
doi = "10.1161/JAHA.118.010321",
language = "English",
volume = "7",
journal = "American Heart Association. Journal. Cardiovascular and Cerebrovascular Disease",
issn = "2047-9980",
publisher = "Wiley-Blackwell",
number = "22",

}

RIS

TY - JOUR

T1 - GLP-1 Is a Coronary Artery Vasodilator in Humans

AU - Clarke, Sophie J.

AU - Giblett, Joel P.

AU - Yang, Lucy L.

AU - Hubsch, Annette

AU - Zhao, Tian

AU - Aetesam-ur-Rahman, Muhammad

AU - West, Nick E. J.

AU - O'Sullivan, Michael

AU - Figg, Nichola

AU - Bennett, Martin

AU - Albrechtsen, Nicolai J. Wewer

AU - Deacon, Carolyn F.

AU - Cheriyan, Joseph

AU - Hoole, Stephen P.

PY - 2018/11/20

Y1 - 2018/11/20

N2 - 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.

AB - 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.

KW - coronary blood flow reserve

KW - coronary microvascular function

KW - coronary microvascular resistance

KW - GLP-1 (glucagon-like peptide 1)

U2 - 10.1161/JAHA.118.010321

DO - 10.1161/JAHA.118.010321

M3 - Journal article

VL - 7

JO - American Heart Association. Journal. Cardiovascular and Cerebrovascular Disease

JF - American Heart Association. Journal. Cardiovascular and Cerebrovascular Disease

SN - 2047-9980

IS - 22

M1 - e010321

ER -

ID: 211810973