Lysyl oxidase-like 2 (LOXL2) knockdown is protective against age-associated vascular stiffening in mice. A: pulse-wave velocity (PWV) with increasing age in the LOXL2+/− mice (n = 12; 7 female, 5 male) and littermate wild-type (WT) mice (n = 10; 5 female, 5 male; n = 20–35 measures per age for each cohort; *P < 0.05, **P < 0.01 vs. WT 1–4 mo old; ‡P < 0.05 vs. WT 4–8 mo old; #P < 0.05, ##P < 0.01 vs. age-matched LOXL2+/− littermates by 2-way ANOVA). B: systolic pressure with increasing age in WT (n = 10; 5 female, 5 male) and LOXL2+/− littermate mice (n = 12; 7 female, 5 male) (n = 25–35 measurements per age group per genotype; **P < 0.01 vs WT 1–4 mo old; ###P < 0.001 vs. age-matched LOXL2 littermates by 2-way ANOVA). C: representative Western blots for LOXL2 protein expression in the aortic matrix of young (Y) and old (O) LOXL2+/− mice and WT littermates (images are representative of n = 5 in each group; old = 20–22 mo old, young = 3–4 mo old; *P < 0.05 vs. old WT by 2-way ANOVA). ECM, extracellular matrix. D: representative confocal microscopy images of intact aortas from 15+-mo-old WT and LOXL2+/− mice (n = 5) stained for LOXL2 (red) and nuclei (blue). Scale bars = 50 μm.