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oai:repisalud.isciii.es:20.500.12105/166982024-05-27T19:32:34Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc 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 author 2022-08 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. 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 Semaglutide treatment attenuates vessel remodelling in ApoE-/- mice following vascular injury and blood flow perturbation.