Fig. 1

Development of age-related pathologic changes in the thoracic aortas of Prkg1^RQ/+ mice. a, b PKG activity was measured in aortic extracts from wild type (WT, blue symbols) and Prkg1^RQ/+ (RQ/+, red symbols) mice using a synthetic peptide (a n = 2 M + 6 F mice per genotype) or by assessing phosphorylation of vasodilator-stimulated protein (VASP) using a phospho-Ser²³⁹-specific antibody (b n = 5 M + 6 F mice per genotype). The PKG inhibitor DT was added as indicated. Three wild type and three mutant aortas are shown in the western blot. c, d Systolic blood pressure measured by telemetry over 24 h in 4-month-old WT and Prkg1^RQ/+ mice (n = 4 male mice per genotype), and mean arterial pressure (MAP) averaged separately during rest (7 a.m.–7 p.m.) and activity (7 p.m.–7 a.m.). e Ultrasound images of thoracic aortas of 12-month-old WT and Prkg1^RQ/+ mice. Measurements were performed at end-diastole, indicated by an arrowhead below the ECG (A = aortic root; B = ascending aorta, and C = aortic arch; RPA=right pulmonary artery; LSA=left subclavian artery). f Diameter of the aortic root, ascending aorta, and aortic arch in 12-month-old WT and Prkg1^RQ/+ mice (n = 6 M + 7 F mice per genotype). g–j Elastin fiber breaks (g), SMC density (h), SMC apoptosis (i), and media collagen content (j) of ascending aorta cross-sections from the animals in panel f were assessed by Van Gieson’s (g), hematoxylin/eosin (h), TUNEL (i), and Masson-Trichrome (j) stains (×80 with 25 µm scale bars in h, i and ×40 with 50 µm bars in g, j). Arrows in g and i point to elastin fiber breaks and some TUNEL-positive nuclei, respectively. Collagen content (j, blue) of aortic media was quantified using ImagePro (A = adventitia; excluded). In panels g and h n = 5 M + 5 F mice and in panels iand j n = 3 M + 3–4 F per genotype. Graphs show means ± SD; *p < 0.05, **p < 0.01, ***p < 0.001 for the indicated comparisons by two-sided Student’s t-test (panels b, f, h, i, j), Mann–Whitney test (g), or two-way ANOVA (panels a, d; ^#p < 0.05 for comparison of basal activity in WT versus RQ/+; ⁺p < 0.05 and ⁺⁺⁺p < 0.001 for comparison of the same condition in the absence versus presence of DT2). In panels g, h, ns = non-signficant. Source data are provided as a Source Data file