Figure 4.

IGF‐1 deficiency impairs hypertension‐induced hypertrophy and structural remodeling in cerebral vessels. (A) Representative confocal micrographs from normotensive (NT) and hypertensive (HT) fixed brains. Hypertension induces hypertrophy of penetrating arterioles in control mice, whereas this adaptive response is impaired in IGF‐1‐deficient mice (green fluorescence: immunostaining for alpha smooth muscle actin). Bar graphs are summary data for calculated wall‐to‐lumen ratios. qPCR data showing mRNA expression of alpha smooth muscle actin and collagens in branches of the middle cerebral arteries isolated from normotensive and hypertensive control and IGF‐1‐deficient mice are shown in panels B and C, respectively. Data are mean ± SEM (n = 4–6 in each group), *P < 0.05 vs. control, ^# P < 0.05 vs. control HT. (D) IGF‐1 deficiency exacerbates hypertension‐induced profragility shift in vascular gene expression signature. Expression of 67 genes related to the pathogenesis of CMHs was determined by qPCR, and vascular fragility signatures (Spearman's ρ) were calculated as described in the Results. A higher ‘fragility signature’ indicates higher expression of profragility genes and lower expression of antifragility regulators. (E) Proposed scheme depicting the mechanisms by which age‐related IGF‐1 deficiency may exacerbate hypertension‐induced microvascular damage, promoting CMHs. Differences between different groups were established using a one‐way ANOVA followed by Tukey's post hoc tests.