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. Author manuscript; available in PMC: 2016 May 4.
Published in final edited form as: JCI Insight. 2016 Apr 21;1(5):e85484. doi: 10.1172/jci.insight.85484

Figure 7. Endothelial Nogo-B regulates de novo synthesis of sphingolipid to affect cardiac pathogenesis through SPT/S1P signaling.

Figure 7

(A) Experimental design related to B and C: WT and Nogo-A/B–deficient mice were i.p. injected with a selective inhibitor of SPT, myriocin (0.3 mg/kg), or vehicle (0.4% fatty acid–free BSA) at the indicated time points. (B) Myocardial permeability assessed 24 hours after surgery by quantifying Evans Blue extravasated into sham-operated or banded WT and Nogo-A/B–deficient hearts. n ≥ 6/group. (C) Inflammation was assessed at 3 days after surgery in WT and Nogo-A/B–deficient mice treated with myriocin or vehicle by immunostaining of CD45 in heart sections and (D) quantification. Scale bar: 100 µm. n ≥ 6 mice/group. Serial echocardiographic analyses of transverse aortic constriction–operated (TAC-operated) WT and Nogo-A/B–deficient mice treated with myriocin (0.3 mg/kg) or vehicle. The parameters measured were (E) left ventricle (LV) end-diastolic diameter (LVDd), (F) LV end systolic diameter (LVDs), and (G) LV fractional shortening (FS). n ≥ 7 mice/vehicle group; n = 7–11 mice/myriocin group. (H) Experimental design: WT mice were i.p. injected with an agonist of S1P1 receptor, SEW2871 (3 mg/kg), or vehicle (DMSO) as shown. (I) Images and (J) quantification of immunohistochemical staining of CD45 in sections of hearts from SEW2871- and vehicle-treated mice 3 days after TAC. n ≥ 7. Scale bar: 100 µm. (K) Serial echocardiographic analyses of TAC-operated mice treated with SEW2871 (3 mg/kg) or vehicle as indicated in H. n = 5 vehicle-treated WT mice; n = 9 SEW2871-treated mice. (L) Analysis of heart weight/tibia length ratios (heart/TL) of hearts from SEW2871- or vehicle-treated mice at 3 months after TAC. n ≥ 5/group. Data are expressed as mean ± SEM. **P < 0.01, ***P < 0.001, #P < 0.05, ###P < 0.001 for myoricin- versus vehicle-treated Nogo-A/B–deficient mice. Statistical significance was evaluated with (B and D) 1-way ANOVA followed by Tukey’s multiple comparison test, (E–G and K) 2-way ANOVA followed by Tukey’s multiple comparison test, and (J and L) unpaired t test.