Extended Data Fig. 3: Axon neogenesis, relation to genotype, age, and cause-effect relationship in adventitia NICIs.

a, NF200⁺ axon density in subclavian and renal arteries in aged (78 weeks) WT vs Apoe^−/− mice with plaque. n = 3 WT, 3 Apoe^−/−. b, Similar NF200⁺ axon density in renal LNs and in splenic red pulp (RP) or white pulp (WP) of aged WT vs Apoe^−/−. n = RLN: 3 WT and 3 Apoe^−/−; spleen: 5 WT and 4 Apoe^−/−. c, Analyses of serum and spleen noradrenaline levels during ageing. n = serum: young: 3 WT, 8 Apoe^−/−; adult: 6 WT, 5 Apoe^−/−; aged: 7 WT, 7 Apoe^−/−; spleen: young: 3 WT, 9 Apoe^−/−; adult: 9 WT, 9 Apoe^−/−; aged: 8 WT, 12 Apoe^−/−. d, NF200⁺, TH⁺, and CGRP⁺ axon density in the aortic root adventitia adjacent to plaques (paraffin sections) in adult (30 weeks) Ldlr^−/− on a Western diet (WD) (n = 5) vs WT mice (n = 4). e, NF200⁺, TH⁺, and CGRP⁺ axon density in the aortic root adventitia (frozen sections) in adult (32 weeks) Apoe^−/− (n = 4) versus WT mice (n = 3) . f, Analysis of aortic arch noradrenaline levels in adult mice. n = 3 WT, 4 Apoe^−/−. g, Representative OR/H image of abdominal aorta of aged humanized Apoe4 knockin mice on high-fat diet (HFD); comparison of serum total cholesterol (n = 16 WT, 21 Apoe^−/−, 8 Apoe4 on chow diet, 10 Apoe4 HFD); and NF200⁺, TH⁺, and CGRP⁺ axon densities in the abdominal aorta adventitia of Apoe4 HFD vs Apoe4 mice (n = 3 Apoe4, 4 Apoe4 HFD). Scale bar, 50 µm. h, Representative OR/H image of abdominal aorta of aged Apoe^−/−/Ltbr^{fl/fl/Tagln-cre} mice, and axon densities in the abdominal adventitia of aged Apoe^−/−/Ltbr^{fl/fl/Tagln-cre} compared to their Apoe^−/− control or WT adventitia. n = 6 WT, 6 Apoe^−/−, 4 Apoe^−/−/Ltbr^{fl/fl/Tagln-cre}. Scale bar, 25 µm. Data are means ± s.e.m. n represents biologically independent animals. Two-way ANOVA with Bonferroni post hoc test (a,b,c,d,e,g); two-sided unpaired Student´s t-test (f); factorial ANOVA with Bonferroni post hoc test (h)

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