{"id":{"repo_id":"cambridge","oai_identifier":"oai:www.repository.cam.ac.uk:1810/294378"},"canonical_url":"https://search.dev.ndltd.org/etd/cambridge/oai:www.repository.cam.ac.uk:1810/294378","repository":{"repo_id":"cambridge","name":"Cambridge University","base_url":"https://api.repository.cam.ac.uk/server/oai/request"},"display":{"title":"The Cardiovascular Effect of GLP-1 in Humans","abstract":"The incretin glucagon-like peptide-1 (GLP-1) abolishes post-ischemic left ventricular contractility (stunning) in humans but the mechanism remains elusive. I hypothesized that this effect is mediated by peripheral or coronary vasodilatation. A comprehensive assessment of the haemodynamic effects of GLP-1 in humans was made, in peripheral arteries using plethysmography, and in coronary arteries using invasive pressure and flow assessments during cardiac catherisation. I also evaluated transmyocardial extraction of GLP-1 and mapped the distribution of the GLP-1 receptor in the human cardiovascular system using immunohistochemistry with an extensively validated monoclonal antibody (mAb). There was no effect of GLP-1 on forearm blood flow, nor were systemic hemodynamics or cardiac output affected, and no binding of GLP-1R mAb was detected in vascular tissue. GLP-1 reduced resting coronary transit time (Tmn (s)) mean (SD): 0.87 (0.39) vs. 0.63 (0.27), p=0.02 and basal microcirculatory resistance (BMR (mmHgs)) mean (SD): 76.3 (37.9) vs. 55.4 (30.4) p=0.02, whereas in controls there was an increase in Tmn: 0.48 (0.24) vs.0.83 (0.41), p<0.001 and BMR: 45.9 (34.7) vs. 66.7 (37.2), p=0.02. GLP-1 R mAb binding was confirmed in ventricular tissue and transmyocardial GLP-1 extraction was observed. Conclusion: GLP-1 causes coronary microvascular dilation and increased flow but does not influence peripheral tone. GLP-1 R immunohistochemistry suggests that GLP-1 coronary vasodilatation is indirectly mediated by a non-receptor mechanism.","abstract_html":"The incretin glucagon-like peptide-1 (GLP-1) abolishes post-ischemic left ventricular contractility (stunning) in humans but the mechanism remains elusive. I hypothesized that this effect is mediated by peripheral or coronary vasodilatation. A comprehensive assessment of the haemodynamic effects of GLP-1 in humans was made, in peripheral arteries using plethysmography, and in coronary arteries using invasive pressure and flow assessments during cardiac catherisation. I also evaluated transmyocardial extraction of GLP-1 and mapped the distribution of the GLP-1 receptor in the human cardiovascular system using immunohistochemistry with an extensively validated monoclonal antibody (mAb). There was no effect of GLP-1 on forearm blood flow, nor were systemic hemodynamics or cardiac output affected, and no binding of GLP-1R mAb was detected in vascular tissue. GLP-1 reduced resting coronary transit time (Tmn (s)) mean (SD): 0.87 (0.39) vs. 0.63 (0.27), p=0.02 and basal microcirculatory resistance (BMR (mmHgs)) mean (SD): 76.3 (37.9) vs. 55.4 (30.4) p=0.02, whereas in controls there was an increase in Tmn: 0.48 (0.24) vs.0.83 (0.41), p&lt;0.001 and BMR: 45.9 (34.7) vs. 66.7 (37.2), p=0.02. GLP-1 R mAb binding was confirmed in ventricular tissue and transmyocardial GLP-1 extraction was observed. Conclusion: GLP-1 causes coronary microvascular dilation and increased flow but does not influence peripheral tone. GLP-1 R immunohistochemistry suggests that GLP-1 coronary vasodilatation is indirectly mediated by a non-receptor mechanism.","abstract_has_math":false,"creators":["Clarke, Sophie"],"institution":"University of Cambridge","degree_name":"Doctor of Philosophy (PhD)","degree_level":"Doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Morrell, Nick","Hoole, Stephen"],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-07-20","date_published":"2019-07-20","updated_at":"2026-07-22T22:24:04Z","subjects":["glucagon-like peptide-1","cardioprotection","GLP-1","coronary haemodynamics"],"languages":["en"],"rights":[],"rights_urls":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/4cc86f35-26b1-47d2-ba4b-b89b3965538e/download","https://www.rioxx.net/licenses/all-rights-reserved/"],"identifier_entries":[]},"links":{"outbound_url":"https://doi.org/10.17863/CAM.41479","outbound_label":"DOI","outbound_source":"dc:identifier.doi"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Morrell, Nick","Hoole, Stephen"]},{"key":"dc:creator","label":"Author","values":["Clarke, Sophie"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.issued","label":"Date","values":["2019-07-20"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Cambridge"]},{"key":"dc:relation.isreferencedby.uri","label":"Dc Relation Isreferencedby URI","values":["https://www.repository.cam.ac.uk/handle/1810/294378"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["glucagon-like peptide-1","cardioprotection","GLP-1","coronary haemodynamics"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/4cc86f35-26b1-47d2-ba4b-b89b3965538e/download","https://www.rioxx.net/licenses/all-rights-reserved/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.doi","label":"DOI","values":["10.17863/CAM.41479"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/3b2d17b2-f00c-41a7-8b56-441dd85a6cee/download"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The incretin glucagon-like peptide-1 (GLP-1) abolishes post-ischemic left ventricular contractility (stunning) in humans but the mechanism remains elusive. I hypothesized that this effect is mediated by peripheral or coronary vasodilatation. A comprehensive assessment of the haemodynamic effects of GLP-1 in humans was made, in peripheral arteries using plethysmography, and in coronary arteries using invasive pressure and flow assessments during cardiac catherisation. I also evaluated transmyocardial extraction of GLP-1 and mapped the distribution of the GLP-1 receptor in the human cardiovascular system using immunohistochemistry with an extensively validated monoclonal antibody (mAb). There was no effect of GLP-1 on forearm blood flow, nor were systemic hemodynamics or cardiac output affected, and no binding of GLP-1R mAb was detected in vascular tissue. GLP-1 reduced resting coronary transit time (Tmn (s)) mean (SD): 0.87 (0.39) vs. 0.63 (0.27), p=0.02 and basal microcirculatory resistance (BMR (mmHgs)) mean (SD): 76.3 (37.9) vs. 55.4 (30.4) p=0.02, whereas in controls there was an increase in Tmn: 0.48 (0.24) vs.0.83 (0.41), p<0.001 and BMR: 45.9 (34.7) vs. 66.7 (37.2), p=0.02. GLP-1 R mAb binding was confirmed in ventricular tissue and transmyocardial GLP-1 extraction was observed. Conclusion: GLP-1 causes coronary microvascular dilation and increased flow but does not influence peripheral tone. GLP-1 R immunohistochemistry suggests that GLP-1 coronary vasodilatation is indirectly mediated by a non-receptor mechanism."]},{"key":"dc:format.checksum.md5","label":"Dc Format Checksum Md5","values":["e25f7979c9787d44e6dbcc6a2022d345","87eda9de84448d1f82354d60eee3eb5f"]},{"key":"dc:title","label":"Title","values":["The Cardiovascular Effect of GLP-1 in Humans"]}]}],"canonical_facts":{"dc:contributor.advisor":["Morrell, Nick","Hoole, Stephen"],"dc:creator":["Clarke, Sophie"],"dc:date.issued":["2019-07-20"],"dc:description.abstract":["The incretin glucagon-like peptide-1 (GLP-1) abolishes post-ischemic left ventricular contractility (stunning) in humans but the mechanism remains elusive. I hypothesized that this effect is mediated by peripheral or coronary vasodilatation. A comprehensive assessment of the haemodynamic effects of GLP-1 in humans was made, in peripheral arteries using plethysmography, and in coronary arteries using invasive pressure and flow assessments during cardiac catherisation. I also evaluated transmyocardial extraction of GLP-1 and mapped the distribution of the GLP-1 receptor in the human cardiovascular system using immunohistochemistry with an extensively validated monoclonal antibody (mAb). There was no effect of GLP-1 on forearm blood flow, nor were systemic hemodynamics or cardiac output affected, and no binding of GLP-1R mAb was detected in vascular tissue. GLP-1 reduced resting coronary transit time (Tmn (s)) mean (SD): 0.87 (0.39) vs. 0.63 (0.27), p=0.02 and basal microcirculatory resistance (BMR (mmHgs)) mean (SD): 76.3 (37.9) vs. 55.4 (30.4) p=0.02, whereas in controls there was an increase in Tmn: 0.48 (0.24) vs.0.83 (0.41), p<0.001 and BMR: 45.9 (34.7) vs. 66.7 (37.2), p=0.02. GLP-1 R mAb binding was confirmed in ventricular tissue and transmyocardial GLP-1 extraction was observed. Conclusion: GLP-1 causes coronary microvascular dilation and increased flow but does not influence peripheral tone. GLP-1 R immunohistochemistry suggests that GLP-1 coronary vasodilatation is indirectly mediated by a non-receptor mechanism."],"dc:format.checksum.md5":["e25f7979c9787d44e6dbcc6a2022d345","87eda9de84448d1f82354d60eee3eb5f"],"dc:identifier.doi":["10.17863/CAM.41479"],"dc:identifier.uri":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/3b2d17b2-f00c-41a7-8b56-441dd85a6cee/download"],"dc:language":["en"],"dc:publisher.institution":["University of Cambridge"],"dc:relation.isreferencedby.uri":["https://www.repository.cam.ac.uk/handle/1810/294378"],"dc:rights":["https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/4cc86f35-26b1-47d2-ba4b-b89b3965538e/download","https://www.rioxx.net/licenses/all-rights-reserved/"],"dc:subject":["glucagon-like peptide-1","cardioprotection","GLP-1","coronary haemodynamics"],"dc:title":["The Cardiovascular Effect of GLP-1 in Humans"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["Doctoral"],"dc:type.qualificationname":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-22T22:24:04Z"}