Abstract 14040: Mechanical Aortic Strain Promotes Expression of Proteolytic Matrix Markers in Abdominal Aortic Aneurysm

Abstract

Introduction: Serum biomarkers for abdominal aortic aneurysms (AAA) have been identified, but the prognostic relevance has remained unclear. Mechanical activation of aortic VSMCs can elicit production of interleukin-6 (IL-6), a cytokine consistently elevated in AAA. Expecting that stressed native aortic cells may drive degenerative remodeling, we hypothesize that biomarkers focused on matrix proteolysis may be elaborated directly from the aortic wall and assessed as an indicator of aortic strain. Methods: AAA was induced in C57Bl/6 mice with peri-adventitial CaCl 2 (n=5). Terminal procedure at 21 days quantified aortic diameter (AoD) by digital microscopy, obtained blood sampling, and collected aortic tissue. Aortic ultrasound (Vevo3100 with VevoVasc Software) was conducted on Days 0 and 21 to assess AoD and aortic strain parameters. Tissue and serum were analyzed to quantify IL-6 and the proteolytic matrix markers: matrix metalloproteinase-9 (MMP-9), Cathepsin S (CtsS), Cystatin C (CysC), and osteoprotegerin (OPG). Aortic VSMCs underwent mechanical stimulation with 12% Stretch and subsequent QPCR for expression of proteolytic matrix markers (n=4). Groups were analyzed by T-test and ANOVA. Results: At 21 days, all mice in AAA group developed true aneurysms by digital microscopy (>50% dilation compared to internal baseline), and this correlated to measurements from transabdominal ultrasound. Aortic strain assessment indicated increased stiffness parameters in AAA (elevated Pulse Wave Velocity, decreased Distensibility, and decreased Global Radial Strain). The AAA group also had significantly elevated levels of IL-6, MMP-9, and OPG (p<0.05 versus Control for each), with a trend toward increased CtsS and CysC. Alternatively, Stretch VSMCs demonstrated upregulated expression of IL-6, CysC, and OPG (p<0.05 vs Static), while the proteases MMP-9 and CtsS remained unchanged. Conclusion: Mechanical activation of aortic VSMCs can stimulate expression of biomarker proteins associated with AAA, but protease production may rely on the inflammatory infiltrate to promote degenerative matrix remodeling. Further investigation into the source of common AAA biomarkers will provide insight for effective integration into patient care.