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. 2017 May 23;8:15557. doi: 10.1038/ncomms15557

Figure 1. HCAR1 regulates VEGFA and capillary density in response to exercise.

Figure 1

(a) Collagen IV-labelled capillaries in the sensorimotor cortex grey matter of wild-type or Hcar1 knockout mice exposed to vehicle injections (control), treadmill exercise or lactate injections, 5 days a week for 7 consecutive weeks. Scale bar, 100 μm. (b) Capillary density (per cent of the total area, normalized to wild-type control) in the sensorimotor cortex. Mean±s.e.m. of n=7 wild-type controls, seven wild-type exercise, six wild-type lactate, five knockout controls, four knockout exercise and six knockout lactate mice. Analysis of variance (ANOVA), P=0.001; Fisher's least significant difference (LSD) post hoc test, **P<0.01; ***P<0.001. (c) Collagen IV-labelled capillaries in the dentate gyrus (DG) of the hippocampus of wild-type or Hcar1 knockout mice treated as in a. Stippled line, the inner border of the granule cell layer (G), circumscribing the sampled area, hilus (H). Scale bar, 50 μm. (d) Capillary density (see b) in the hilus. Mean±s.e.m. of n mice (n=4–7, as specified below for diameters). ANOVA, P=0.022; Fisher's LSD post hoc test, **P<0.01. Capillary external diameters (μm) in the same areas were unchanged (mean±s.e.m. (n)): wild-type control 5.8±0.2 (6), wild-type exercise 5.7±0.1 (7), wild-type lactate 5.7±0.2 (6), knockout control 5.8±0.3 (5), knockout exercise 6.0±0.1 (4), knockout lactate 5.8±0.2 (6). ANOVA, P=0.93. (e) Quantification of VEGFA in hippocampus of wild-type animals. Data are relative to α-tubulin (α-tub), normalized to wild-type control, mean±s.e.m. of n=4 wild-type control mice, five wild-type exercised mice and six mice treated with lactate, ANOVA, P=0.001; Dunnetts's T3 post hoc test, *P<0.05, ***P<0.001. (f) Quantification of VEGFA in hippocampus of knockout animals presented as in e. n=6 mice per group. ANOVA, P=0.88. (g) Western blots of VEGFA underlying e,f (uncropped scans shown in Supplementary Fig. 6a).