Abstract 18373: Differential Effects of Hypertension and Aneurysm on Stiffness Properties of the Abdominal Aorta

Abstract

Introduction: The serum and glucocorticoid inducible kinase-1 (SGK-1) can contribute to matrix remodeling in murine models of hypertension (HTN) and abdominal aortic aneurysm (AAA), a potential biomechanical link between these aortopathies. Utilizing aortic stiffness as a marker of pathologic remodeling. Hypothesis: We hypothesize that HTN causes an SGK-1 dependent increase in aortic stiffness to amplify AAA growth. Methods: AngiotensinII (AngII) infusion induced HTN in C57Bl/6 mice (WT;1.46mg/kg/day) with subset groups treated + periadventitial CaCl2 to induce AAA and + infusion of the specific SGK-1 inhibitor EMD638683 (2.5mg/kg/day;n=2-4 each). Abdominal aortic ultrasound was conducted on Day 0 and Day 21 to measure stiffness parameters (radial strain(RS), distensibility(D), pulse propagation velocity(PPV)). Aortic diameter (AoD) was obtained by ultrasound and systolic blood pressures (SBP) were measured by Coda tail cuff. Results: This HTN model has consistently resulted in >30% increase in SBP and AAA induction did not effect SBP. Although the WT+AngII+AAA mice had 66+8% increase in AoD, dilation was not amplified beyond that of the WT+AAA mice (72+7%, p=NS). Treatment with EMD had no impact on SBP, but did significantly reduce AAA growth (WT+AAA+EMD=29+5%; WT+AngII+AAA+EMD= 24+3%), therefore despite ongoing mechanical tension, SGK-1 inhibition abrogated a pathway necessary for degenerative remodeling. Accordingly, aortic stiffness was differentially altered in HTN versus AAA. As indictors of increased stiffness, D decreased with HTN (p<0.05 vs Day 0) and RS decreased with AAA (p<0.05 vs Day 0), but SGK-1 inhibition had no effect, indicating that the matrix remodeling driving these mechanical parameters was not SGK-1 dependent. Conversely, PPV was increased in both aortopathies (WT+AAA, WT+AngII, WT+AngII+AAA; each p<0.05 vs Day 0) but EMD infusion prevented elevation in PPV, suggesting SGK-1-dependent preservation of contractility. Conclusions: Although concurrent induction of HTN and AAA did not amplify AAA growth, these aortopathies differentially impacted aortic stiffness. Tracking PPV as an indicator of pathologic SGK-1 activity may represent a pharmacological target to abrogate dysfunctional aortic remodeling.