Introduction: Hypertension is a known predictor of cardiovascular morbidity due to dysfunctional matrix remodeling which promotes aortic stiffness, but achieving normotension does not eliminate this risk. Prior work has demonstrated mechanical sensitivity of the serum and glucocorticoid inducible kinase-1 (SGK-1) in vascular disease through inflammatory signaling. We hypothesize that biomechanical signals promote activity of SGK-1 in VSMCs to drive expression of key pathologic matrix markers (PMMs). Methods: Aortic rings were harvested from C57BI/6 WT and smooth muscle specific SGK-1 knockout (SMC-SGK-1KO +/- ) mice. Rings were placed on a myograph in a physiologic salt solution and exposed to experimentally derived optimal tension (baseline OT, 1.5g) or OT+30% (1.95g) for 6 hrs (n=4-6). WT Rings were homogenized to determine SGK-1 and pSGK-1 abundance by immunoblotting. Replicates were treated ±AngII and ±EMD638683 (EMD; a specific SGK-1 inhibitor). RNA extraction enabled QPCR for select PMMs (Interleukin-6 (IL-6), Cathepsin S (CtsS), Cystatin C (CysC), Tenascin C (TNC)). Statistical comparisons utilized ANOVA with significance set at p<0.05. Results: There was a significant increase in pSGK-1 abundance and in the pSGK-1/SGK-1 ratio in the WT aortic rings at OT+30%, confirming that mechanical tension promoted SGK-1 activity. IL-6 and CysC expression was augmented in the WT OT+30% (p<0.05 vs WT OT for each), but returned to baseline in the presence of EMD, implicating that SGK-1 may play a causative role for these effects. While expression of all PMMs increased with OT+AngII or OT+30%+AngII, only IL-6 demonstrated a synergistic effect with biomechanical stimulation. In aortic rings from SMC-SGK-1KO +/- animals, the response to mechanical stimulation was blunted for all PMMs, further supporting a role for SGK-1 in pathologic mechanical signaling. Conclusion: Mechanical tension on the aortic wall can increase SGK-1 activity, correlating to expression of key mediators of pathologic vascular remodeling. These novel findings suggest that SGK-1 may be a druggable target to reduce aortic stiffness in the setting of hypertensive disease.