Abstract 808: Functional Assays of von Willebrand Factor (VWF) and VWF-cleaving Protease (ADAMTS13) Activity in Acute Myocardial Infarction
Backgrounds: The hemostatic activity of von Willebrand factor (VWF) is strongly dependent on its multimeric structure, with the highest activity in large multimers secreted from endothelial cells. Recently, metalloprotease that cleaves large VWF multimers has been identified, namely, VWF-cleaving protease (ADAMTS13). We recently reported reduced plasma ADAMTS13 levels in acute myocardial infarction (AMI), and in addition, that the early decrease of ADAMTS13 levels was an important predictor of future thrombotic events after AMI. In this study, we examined the functional assays of VWF and ADAMTS13 activity using the plasma samples obtained from AMI patients, and also the relationship between the VWF and ADAMTS13 activity levels in AMI.
Methods and Results: The subjects comprised 33 patients with AMI, 33 with stable exertional angina (SEA) and 30 with chest pain syndrome (CPS). Functional assay for VWF activity was performed by analyzing the binding to the collagen type III. ADAMTS13 activity was measured by detecting fluorescence intensity obtained from the mixture with FRETS-VWF73. Plasma VWF antigen levels (mU/mL) increased significantly in patients with AMI compared to the SEA and CPS groups on admission (2214 ± 109, 1445 ± 93 and 1425 ± 76, respectively; P<0.0001 in AMI vs. SEA and CPS). VWF functional assay revealed that VWF activity (mU/mL) that bound to collagen type III significantly increased in patients with AMI compared to the SEA and CPS groups (2279 ± 152, 1713 ± 104 and 1717 ± 72, respectively; P<0.01 in AMI vs. SEA and CPS). Plasma ADAMTS13 antigen and activity levels (mU/mL) were significantly lower in patients with AMI than in those with SEA and CPS (829 ± 33, 996 ± 31 and 967 ± 31 in antigen levels, respectively; P<0.01 in AMI vs. SEA and CPS, 754 ± 31, 893 ± 27 and 936 ± 29 in activity levels, respectively; P<0.01 in AMI vs. SEA and CPS). Furthermore, there were significant inverse correlations between functional VWF and ADAMTS13 activity levels (r = 0.400, P<0.0001; respectively).
Conclusions: These findings suggested that the decreased ADAMTS13 activity might be due to its consumption by increased VWF activity in AMI patients. The treatments that increase the ADAMTS13 activity might contribute to stabilizing the platelet thrombus formation in AMI.