2026-05-16T22:13:01Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/166982024-05-27T19:32:34Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Jensen, Ditte Marie
author
Skovsted, Gry Freja
author
Bonde, Mathilde Frederikke Bjørn
author
Bentzon, Jacob Fog
author
Rolin, Bidda
author
Franck, Grégory
author
Ougaard, Maria Katarina Elm
author
Voetmann, Louise Marie
author
Bachmann, Julian Christoffer
author
Uryga, Anna
author
Pyke, Charles
author
Kirk, Rikke Kaae
author
Hvid, Henning
author
Knudsen, Lotte Bjerre
author
Lykkesfeldt, Jens
author
Nyberg, Michael
2023-11-17T15:17:55Z
2023-11-17T15:17:55Z
2022-08
Atheroscler Plus. 2022 Jun 4:49:32-41.
10.1016/j.athplu.2022.05.004
2667-0895
Atherosclerosis plus
36644202
http://hdl.handle.net/20.500.12105/16698
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.
eng
Semaglutide treatment attenuates vessel remodelling in ApoE-/- mice following vascular injury and blood flow perturbation.
journal article
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Semaglutide treatment_Atheroscler Plus_2022.pdf
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Semaglutide treatment_Atheroscler Plus_2022.pdf.txt