It points to their importance in hemostasis, bleeding disorders, and the developing field of therapeutic application of ADAMTS-13 as an antithrombotic agent in obstructive microvascular thrombosis and in cardiovascular disease.
Low ADAMTS13 activity is associated with an increased risk of cardiovascular disease, which is generally attributed to its proteolytic effects on Von Willebrand factor (VWF).
Induced substrate promiscuity will be important as ADAMTS-13 variants are developed as potential therapeutic agents against thrombotic thrombocytopenic purpura (TTP) and other cardiovascular diseases.
An association between high VWF levels and cardiovascular disease has frequently been reported, and more recently also an association has been observed between low ADAMTS13 levels and arterial thrombosis.
Recent studies have shown that increased plasma levels of Von Willebrand factor (VWF) and reduced plasma levels of enzyme ADAMTS13 are associated with diabetic nephropathy and an increased risk of developing cardiovascular disease, suggesting that these markers of hypercoagulability may contribute to an increased risk of cardiovascular disease in diabetic patients with impaired renal function.
Modeling ADAMTS13-von Willebrand factor interaction: Implications for oxidative stress-related cardiovascular diseases and type 2A von Willebrand disease.
Deficiency of functional ADAMTS13 is associated with a number of disease pathologies including thrombotic thrombocytopenic purpura, cardiovascular disease and inflammation.