Effect of aging and long-term high fat diet feeding on aortic stiffness and blood pressure of wild-type and G6PDS188Frats and VAT-derived CCL5 positively correlates with aortic stiffness and incubation of aorta with CCL5 augments elastic modulus.A–C, aging increased pulse wave velocity (PWV; index of aortic stiffness) and systolic and diastolic blood pressure in both genotypes. However, diastolic pressure in older G6PDS188F was significantly lower than in age-matched wild-type (WT) rats. D–F, HFD feeding for 8 months did not increase PWV and blood pressure in older wild-type rats, and blood pressure in older G6PDS188F rats, as compared with age-matched rats on a normal chow (NC) diet. However, HFD feeding increased PWV in G6PDS188F rats as compared with age-matched rats on the NC diet. G and H, representative H&E and Mason’s Trichrome staining of aorta isolated from wild-type and G6PDS188F rats fed with high-fat diet (HFD) or normal chow (NC) is shown. H&E staining images show hypertrophy of the medial layer in HFD-fed rats and Manson’s Trichrome staining shows collagen and fibrosis of the aorta is less pronounced in G6PDS188F rats as compared with wild-type rats on NC but not on long-term HFD. Images were reused to demonstrate rigor and reproducibility in Fig. S10. I and J, Pearson’s correlation shows a positive correlation between visceral adipose tissue (VAT) volume-systolic blood pressure (SBP) and -pulse wave velocity (PWV). K and L, Pearson’s correlation shows a positive correlation between VAT-derived CCL5-SBP and -PWV in G6PDS188F rats but not wild-type rats. M, isolated aorta from wild-type and G6PDS188F rats was incubated with CCL5 (1 ng/ml) ex vivo and after 72 h elastic modulus was determined by atomic force microscopy. Application of CCL5 increased elastic modulus. Two-way ANOVA with post hoc Tukey’s multiple comparison test were used to compare multiple groups. ∗p < 0.05; ∗∗p < 0.01; ∗∗∗p < 0.005; and ∗∗∗∗p < 0.001.