Fig. 5: Deletion of Nogo-A/B protects from vascular dysfunction by preserving sphingolipid levels.

A Vascular function of mesenteric arteries (MA) was assessed in WT or Nogo-A/B-deficient mice fed with SD or HFD for 6 months by using the pressure myograph system (Danish MyoTechnology, Aarhus, Denmark), (Created in BioRender. Di Lorenzo, A. (2025) https://BioRender.com/i50g226). B Ach-mediated vasodilation (WT SD n = 6 mice, Nogo-A/B-deficient SD n = 4 mice, WT HFD n = 6 mice, Nogo-A/B-deficient HFD n = 6 mice); C Flow-induced vasodilation (WT SD n = 6 mice, Nogo-A/B-deficient SD n = 5 mice, WT HFD n = 5 mice, Nogo-A/B-deficient HFD n = 6 mice). HFD MA of WT or Nogo-A/B-deficient mice were incubated with W146 (300 nM, 30 min), an S1P1 inhibitor (WT SD n = 6 mice, Nogo-A/B-deficient SD n = 5 mice, WT HFD n = 5 mice, Nogo-A/B-deficient HFD n = 6 mice, WT HFD n = 4 mice and Nogo-A/B-deficient HFD n = 3 mice treated with W146); D, E PE-induced vasoconstriction (WT SD n = 6 mice, Nogo-A/B-deficient SD n = 4 mice, WT HFD n = 6 mice, Nogo-A/B-deficient HFD n = 6 mice); F myogenic tone (WT SD n = 7 mice, Nogo-A/B-deficient SD n = 4 mice, WT HFD n = 6 mice and Nogo-A/B-deficient HFD n = 6 mice); and G AngII-induced vasoconstriction (WT SD n = 4 mice, Nogo-A/B-deficient SD n = 4 mice, WT HFD n = 4 mice and Nogo-A/B-deficient HFD n = 4 mice) in MA. LC–MS/MS quantification of H total and I specific Cer, and of J total and K specific SM in MA (WT HFD n = 11 mice, Nogo-A/B-deficient HFD n = 9 mice). Data are expressed relative to WT HFD. L WB analysis of p-MLC (Ser19), MLC, p-MYPT1 (Thr696), MYPT1 and NOGO-B in MA from obese WT or Nogo-A/B-deficient mice, with or without AngII stimulation (10⁻⁷M, 20 s) and M, N relative quantification (n = 4 mice per group). Data were expressed as mean ± SEM. *p ≤ 0.05, **p ≤ 0.01, ***p ≤ 0.001. Statistical analysis was performed with two-way ANOVA with Sidak multiple comparisons test (B–G) and unpaired t-test two tailed (H–K, M, N). Source data are provided as a Source Data file.