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Semaglutide treatment attenuates vessel remodelling in ApoE−/− mice following vascular injury and blood flow perturbation
BACKGROUND AND AIMS: Randomized clinical studies have shown a reduction in cardiovascular outcomes with glucagon-like peptide 1 receptor agonist (GLP-1RA) treatment with the hypothesized mechanisms being an underlying effect on atherosclerosis. Here, we aimed to assess the pharmacological effects of...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9833261/ https://www.ncbi.nlm.nih.gov/pubmed/36644202 http://dx.doi.org/10.1016/j.athplu.2022.05.004 |
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author | Jensen, Ditte Marie Skovsted, Gry Freja Bonde, Mathilde Frederikke Bjørn Bentzon, Jacob Fog Rolin, Bidda Franck, Grégory Ougaard, Maria Katarina Elm Voetmann, Louise Marie Bachmann, Julian Christoffer Uryga, Anna Pyke, Charles Kirk, Rikke Kaae Hvid, Henning Knudsen, Lotte Bjerre Lykkesfeldt, Jens Nyberg, Michael |
author_facet | Jensen, Ditte Marie Skovsted, Gry Freja Bonde, Mathilde Frederikke Bjørn Bentzon, Jacob Fog Rolin, Bidda Franck, Grégory Ougaard, Maria Katarina Elm Voetmann, Louise Marie Bachmann, Julian Christoffer Uryga, Anna Pyke, Charles Kirk, Rikke Kaae Hvid, Henning Knudsen, Lotte Bjerre Lykkesfeldt, Jens Nyberg, Michael |
author_sort | Jensen, Ditte Marie |
collection | PubMed |
description | BACKGROUND AND AIMS: Randomized clinical studies have shown a reduction in cardiovascular outcomes with glucagon-like peptide 1 receptor agonist (GLP-1RA) treatment with the hypothesized mechanisms being an underlying effect on atherosclerosis. Here, we aimed to assess the pharmacological effects of semaglutide in an atheroprone murine model that recapitulates central mechanisms related to vascular smooth muscle cell (VSMC) phenotypic switching and endothelial dysfunction known to operate within the atherosclerotic plaque. METHODS: In study A, we employed an electrical current to the carotid artery in ApoE−/− mice to induce severe VSMC injury and death, after which the arteries were allowed to heal for 4 weeks. In study B, a constrictive cuff was added for 6 h at the site of the healed segment to induce a disturbance in blood flow. RESULTS: Compared to vehicle, semaglutide treatment reduced the intimal and medial area by ∼66% (p = 0.007) and ∼11% (p = 0.0002), respectively. Following cuff placement, expression of the pro-inflammatory marker osteopontin and macrophage marker Mac-2 was reduced (p < 0.05) in the semaglutide-treated group compared to vehicle. GLP-1R were not expressed in murine carotid artery and human coronary vessels with and without atherosclerotic plaques, and semaglutide treatment did not affect proliferation of cultured primary human VSMCs. CONCLUSIONS: Semaglutide treatment reduced vessel remodelling following electrical injury and blood flow perturbation in an atheroprone mouse model. This effect appears to be driven by anti-inflammatory and -proliferative mechanisms independent of GLP-1 receptor-mediated signalling in the resident vascular cells. This mechanism of action may be important for cardiovascular protection. |
format | Online Article Text |
id | pubmed-9833261 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-98332612023-01-12 Semaglutide treatment attenuates vessel remodelling in ApoE−/− mice following vascular injury and blood flow perturbation Jensen, Ditte Marie Skovsted, Gry Freja Bonde, Mathilde Frederikke Bjørn Bentzon, Jacob Fog Rolin, Bidda Franck, Grégory Ougaard, Maria Katarina Elm Voetmann, Louise Marie Bachmann, Julian Christoffer Uryga, Anna Pyke, Charles Kirk, Rikke Kaae Hvid, Henning Knudsen, Lotte Bjerre Lykkesfeldt, Jens Nyberg, Michael Atheroscler Plus Full Length Article BACKGROUND AND AIMS: Randomized clinical studies have shown a reduction in cardiovascular outcomes with glucagon-like peptide 1 receptor agonist (GLP-1RA) treatment with the hypothesized mechanisms being an underlying effect on atherosclerosis. Here, we aimed to assess the pharmacological effects of semaglutide in an atheroprone murine model that recapitulates central mechanisms related to vascular smooth muscle cell (VSMC) phenotypic switching and endothelial dysfunction known to operate within the atherosclerotic plaque. METHODS: In study A, we employed an electrical current to the carotid artery in ApoE−/− mice to induce severe VSMC injury and death, after which the arteries were allowed to heal for 4 weeks. In study B, a constrictive cuff was added for 6 h at the site of the healed segment to induce a disturbance in blood flow. RESULTS: Compared to vehicle, semaglutide treatment reduced the intimal and medial area by ∼66% (p = 0.007) and ∼11% (p = 0.0002), respectively. Following cuff placement, expression of the pro-inflammatory marker osteopontin and macrophage marker Mac-2 was reduced (p < 0.05) in the semaglutide-treated group compared to vehicle. GLP-1R were not expressed in murine carotid artery and human coronary vessels with and without atherosclerotic plaques, and semaglutide treatment did not affect proliferation of cultured primary human VSMCs. CONCLUSIONS: Semaglutide treatment reduced vessel remodelling following electrical injury and blood flow perturbation in an atheroprone mouse model. This effect appears to be driven by anti-inflammatory and -proliferative mechanisms independent of GLP-1 receptor-mediated signalling in the resident vascular cells. This mechanism of action may be important for cardiovascular protection. Elsevier 2022-06-04 /pmc/articles/PMC9833261/ /pubmed/36644202 http://dx.doi.org/10.1016/j.athplu.2022.05.004 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Full Length Article Jensen, Ditte Marie Skovsted, Gry Freja Bonde, Mathilde Frederikke Bjørn Bentzon, Jacob Fog Rolin, Bidda Franck, Grégory Ougaard, Maria Katarina Elm Voetmann, Louise Marie Bachmann, Julian Christoffer Uryga, Anna Pyke, Charles Kirk, Rikke Kaae Hvid, Henning Knudsen, Lotte Bjerre Lykkesfeldt, Jens Nyberg, Michael Semaglutide treatment attenuates vessel remodelling in ApoE−/− mice following vascular injury and blood flow perturbation |
title | Semaglutide treatment attenuates vessel remodelling in ApoE−/− mice following vascular injury and blood flow perturbation |
title_full | Semaglutide treatment attenuates vessel remodelling in ApoE−/− mice following vascular injury and blood flow perturbation |
title_fullStr | Semaglutide treatment attenuates vessel remodelling in ApoE−/− mice following vascular injury and blood flow perturbation |
title_full_unstemmed | Semaglutide treatment attenuates vessel remodelling in ApoE−/− mice following vascular injury and blood flow perturbation |
title_short | Semaglutide treatment attenuates vessel remodelling in ApoE−/− mice following vascular injury and blood flow perturbation |
title_sort | semaglutide treatment attenuates vessel remodelling in apoe−/− mice following vascular injury and blood flow perturbation |
topic | Full Length Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9833261/ https://www.ncbi.nlm.nih.gov/pubmed/36644202 http://dx.doi.org/10.1016/j.athplu.2022.05.004 |
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