BS57 Assessing proteoglycans and proteoglycanases as biomarkers for thoracic aortic aneurysms

Background Thoracic Aortic Aneurysm (TAA) is a disease with significant morbidity and mortality. The aneurysm is asymptomatic, and patients often present to the emergency department after a dissection. A reliable biomarker is required to diagnose the condition early to direct the patient to the appropriate services. TAA is characterised by proteoglycan accumulation which are normally found in the extracellular matrix (ECM) of the medial layer. This may be due to impaired activity of intrinsic proteases A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTS) 4 and 5. We aimed to find a circulating proteoglycan-based biomarker associated with abnormal material properties of the diseased aortic wall. Methods ADAMTS-generated fragment ‘versikine’, ADAMTS4, ADAMTS5, ADAMTS13 and von Willebrand Factor (vWF) were measured in the plasma of patients with TAA (n=48) and healthy controls (n=23) using Enzyme-Linked Immunosorbent Assays. Patients with connective tissue disease (CTD) and bicuspid aortic valve were excluded from the study. Mann-Whitney U test was used to compare the analyte plasma levels between the groups and Spearman Rank to test for correlation. Receiver-operator characteristics curve analysis was used to generate specificity and sensitivity values. In five patients, explanted TAA samples from surgery were processed to extract proteoglycans using 4M Guanidine HCl and purified by Diethylaminoethyl chromatography. Western Blot was used to qualitatively analyse the fragments. Results Versikine plasma concentration was higher in TAA patients compared to controls (34.23±3.83 vs 10.05±1.15 ng/mL, p<0.0001). In TAA patients, versikine concentration was negatively correlated with the aortic diameter (r=-0.3712, p=0.0218) and outer curve thickness (r=-0.3819, p=0.0493). ADAMTS4 plasma concentration was lower in TAA patients compared to controls (11.02±2.88 vs 25.02±5.07 ng/mL, p=0.0114). ADAMTS5, ADAMTS13 and vWF concentrations were similar in both groups. Versikine plasma levels could identify TAA with a sensitivity of 68.1% and specificity of 95.6%. In addition, high levels of versikine were present in the aneurysmal aortic tissue. Conclusion Versikine levels are higher in the plasma of TAA patients which may be due to the high turnover of versican in the aortic tissue. Versikine levels correlated with both aortic diameter and outer curve aortic thickness. Lower ADAMTS4 levels suggest reduced proteolysis which may contribute to the accumulation of proteoglycans in the tissue. Versikine has potential to become a reliable biomarker for diagnosing a TAA. Larger trials including CTD and bicuspid valve patients are required to validate versikine as a biomarker and test its’ ability to predict aortic diameter changes over time. Conflict of Interest none