Could site-specific glycation of Von Willebrand factor serve as a biomarker for macrovascular disease in diabetes?

Abstract

Cardiovascular disease (CVD) is the leading cause of mortality among diabetic patients. Glycation is a non-enzymatic, post translational process where sugars bind to proteins, and it is accelerated in diabetes. Glycation may alter protein structure and function. Von Willebrand Factor (VWF) is a key player in coagulation, and its glycation could potentially exacerbate the pro-thrombotic state associated with diabetes. We hypothesize that glycation of VWF contributes to the progression of macrovascular complications by altering its interactions with key hemostatic partners, such as Factor VIII, platelets (via GPIbα binding), and ADAMTS-13 thereby promoting hypercoagulability and endothelial dysfunction. This hypothesis highlights a functional link between chronic hyperglycemia and macrovascular complications in diabetes. To test this hypothesis, mapping glycation of sites of VWF using mass spectrometry and validating its role as a biomarker using patient-derived samples and high-throughput assays is proposed. If confirmed, this mechanism could provide a novel biomarker for the early detection of high-risk patients and open up new therapeutic targets to manage cardiovascular complications aimed at mitigating cardiovascular disease and improving patient outcomes.