Journal of Vascular Diseases · Published 2026-02-16 · DOI 10.3390/jvd5010010
<b>Background/Objective:</b> Activity of SGK-1 has been associated with mechanical aspects of vascular remodeling and matrix stiffening has been a known characteristic of AAA. We hypothesis that VSMC-specific SGK-1 activity is vital to growth of AAA and contributes to progressive aortic stiffness. <b>Methods:</b> C57Bl/6 and SMC-SGK-1KO<sup>+/−</sup> mice underwent AAA induction vs Sham on day 0. A subset of C57Bl/6 mice had pump implantation to treat with EMD638683. Aortic ultrasound images were obtained on Day 0 and Day 21 and analyzed for mechanical parameters. At terminal procedure the infrarenal aorta was harvested for immunoblot analysis. <b>Results:</b> At Day 21, C57Bl/6+AAA mice showed growth of 72.27% ± 2.2% versus the C57Bl/6+Sham (<i>p</i> < 0.0001) with associated 3.71 ± 1.15-fold increase in SGK-1 activity (<i>p</i> = 0.001). C57Bl/6+AAA+EMD mice demonstrated growth of 23.68% ± 2.82% (<i>p</i> = 0.0452) with no significant change in SGK-1 activity. SMC-SGK1-KO<sup>+/−</sup>+AAA mice had growth of 28.20% ± 3.74% compared to SMC-SGK1-KO<sup>+/−</sup>+Sham (<i>p</i> = 0.004) with increased SGK-1 activity (<i>p</i> = 0.0303). Radial strain was significantly reduced in the C57Bl/6+AAA (<i>p</i> = 0.0062) and C57Bl/6+AAA+EMD (<i>p</i> = 0.0135) when compared to C57Bl/6+Sham. Distensibility was significantly reduced in C57Bl/6+AAA (<i>p</i> = 0.01). Pulse propagation velocity (PPV) was significantly elevated in C57Bl/6+AAA mice (<i>p</i> < 0.0001) but inhibited by EMD therapy (<i>p</i> = 0.0007 vs. C57Bl/6+AAA). SMC-SGK1-KO<sup>+/−</sup> +AAA mice showed significant reductions in radial strain (<i>p</i> = 0.0011) and distensibility (<i>p</i> = 0.0233) with a modest, but significant, increase in PPV (<i>p</i> = 0.0148). <b>Conclusions:</b> SGK-1 inhibition attenuated AAA growth and preserved vascular function. Targeting this pathway may provide a directed medical therapy for AAA and warrants further investigation.
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