Portal de Periódicos da CAPES

Oral presentations

2023; Wiley; Volume: 239; Issue: S728 Linguagem: Inglês

10.1111/apha.14042

1748-1716

Rashika Sivakumar, Simin, Berenji Ardestani, Vladimir V. Matchkov, Lana Kralj, Nejka Potočnik, Helena Lenasi, Gry Freja Skovsted, Alex Aupetit, Karl Björling, Kristian Agmund Haanes, Susanne Syberg, Niklas, Rye Jørgensen, Kristine Freude, James, Todd Pearson, Lars, Lars Jørn Jensen, Joakim Bastrup, Samuel N. Baldwin, Jennifer van der Horst, Olga Kudryavtseva, Salomé Rognant, Johs Dannesboe, Anthony Mozzicato, Morten B. Thomsen, Thomas A. Jepps, Florencia Cabrera-Cabrera, Annela Avarlaid, Indrek Koppel, Tõnis Timmusk, Ieva Sarapinienė, Rokas Mickus, Valeryia Mikalayeva, Vytautas Raškevičius, Rytis Prekeris, Vytenis, Arvydas Skeberdis, Ornella Manfra, Xin Shen, Johannes Hell, Christian Soeller, William E. Louch, Simona Kavaliauskiene, Victoria Becker, Oda Stødle, Vilde Arntzen Engdal, Marco Vindas, Michael Frisk, Ida B. Johansen,

Introduction: Sortillin-related VPS10P containing receptor (SorCS2) is expressed in neurons and other tissues during development where it mediates trafficking of target proteins between cell membrane and intercellular compartments.It has also been suggested that SorCS2 modulates signal transduction.SorCS2 is also upregulated in vascular wall under pathological conditions, e.g., atherosclerosis.The aim of this study is to elucidate the contribution of endothelial and smooth muscle SorCS2 to the vascular function.Method: We compared mesenteric small arteries (MSA) from endothelium-and smooth-muscle-specific knockouts for SorCS2 with matching controls ex vivo in isometric myograph.The controls were mice with floxed SorCS2 gene but without any Cre-recombinase expression.The endothelial-specific SroCS2 knockout was constitutive knockout with Cre expression controlled by Tie2 promoter.Cre expression was controlled by estrogen receptor type 2 under smooth-muscle-myosinheavy-chain promoter and smooth-muscle-specific knockout was induced by tamoxifen treatment.Vascular compliance, inner arterial diameters, noradrenalineinduced contraction, acetylcholine-induced relaxation and relaxation to NO donor, sodium nitroprusside were compared. Results:The endothelial-specific SorCS2 knockout MSA showed no association with vascular remodeling and changes in the contractile responses but demonstrated reduced sensitivity to sodium nitroprusside in comparison with the controls.The smooth-muscle-specific SorCS2 knockout MSA had no changes in both acetylcholine-and sodium-nitroprusside-induced relaxations but showed decreased noradrenaline-induced contraction and compliance in comparison with the control arteries.Conclusion: Our findings from the cell-specific models indicate that SorCS2 contributes to endothelial-and smooth muscle cell functions in murine mesenteric arteries.