Thoracic aortic aneurysms in VSMC-targeted, Secisbp2 knockout mice. ASecisbp2 mRNA expression in aortic media or adventitia tissue isolated from wild-type (+/+: grey), heterozygous (+/−: orange) and homozygous (−/−: blue) VSMC-specific Secisbp2 knockout mice. Statistics: ordinary one-way ANOVA with adjusted p values (Tukey’s multiple comparison test), each bar represents the mean (n = 4–7 animals per genotype), error bars represent SEM. B Expression of selenoproteins (Gpx4, SelenoO, Sephs2) or β-actin (loading control) in aortic media tissue isolated from wild-type (+/+), heterozygous (+/−) and homozygous (−/−) VSMC-specific Secisbp2 knockout mice (n = 2 animals per genotype). C and D Percent survival of animals (C) or aortic aneurysm frequency (D), following angiotensin II infusion of wild type (+/+: grey), heterozygous (+/−: orange) or homozygous (−/−: blue) VSMC-specific, Secisbp2 knockout mice. Statistics: Two sample Z test of proportions, two-tail for −/− vs. +/− plus +/+ group comparison (n = 10–14 animals per genotype). E Histology of haematoxylin and eosin (H&E)-stained TAA (from angiotensin II-treated homozygous VSMC-specific Secisbp2 knockout mouse showing laminated thrombus within the vessel wall (asterisk) and cystic medial necrosis (arrowed inset). n = 10 independent experiments with similar results, scale bars = 300 μm. F Histology of thoracic aorta stained with H&E, EVG, Alcian Blue and von Kossa stains, or immunohistochemistry for 8-oxo-G, γ-H2AX or TUNEL with SMA from wild-type (+/+), heterozygous (+/−) and homozygous (−/−) VSMC-specific Secisbp2 knockout mice exposed to angiotensin II (as detailed in Supplementary Fig. 9B). Insets show high power views of outlined areas. Arrows indicate γ-H2AX or TUNEL-positive, αSMA-expressing cells, n = 9–14 independent experiments with similar results, scale bars = 300 μm. G–I Mean number of 8-oxo-G (G), γ-H2AX (H) and TUNEL (I)-positive cells in thoracic aorta sections of wild-type (+/+: grey), heterozygous (+/−: orange) and homozygous (−/−: blue) VSMC-specific Secisbp2 knockout mice. *p < 0.05 1-Way ANOVA. n = 9–14 mice 5 sections/mouse. Statistics: ordinary one-way ANOVA with adjusted p values (Tukey’s multiple comparison test), each bar represents the mean (n = 9–14 mice, 5 sections/mouse), error bars represent SEM. The genetic background of the Myh11-CreERt2/Secisbp2flox/flox mice generates only male, VSMC-specific knockout animals (C57BL/6N, 13 weeks old). Source data are provided as a Source Data file.
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