Summary
Type 2 diabetes mellitus (T2DM) is associated with increased coagulability and vascular
complications. Circulating microparticles (MPs) are involved in thrombosis, inflammation,
and angiogenesis. However, the role of MPs in T2DM vascular complications is unclear.
We characterised the cell origin and pro-coagulant profiles of MPs obtained from 41
healthy controls and 123 T2DM patients with coronary artery disease, retinopathy and
foot ulcers. The effects of MPs on endothelial cell coagulability and tube formation
were evaluated. Patients with severe diabetic foot ulcers expressed the highest levels
of MPs originated from platelet and endothelial cells and negatively-charged phospholipidbearing
MPs. MP coagulability, calculated from MP tissue factor (TF) and TF pathway inhibitor
(TFPI) ratio, was low in healthy controls and in diabetic retinopathy patients (<0.7)
but high in patients with coronary artery disease and foot ulcers (>1.8, p≥0.002).
MPs of all T2DM patients induced a more than two-fold increase in endothelial cell
TF (antigen and gene expression) but did not affect TFPI levels. Tube networks were
longest and most stable in endothelial cells that were incubated with MPs of healthy
controls, whereas no tube formation occurred in MPs of diabetic patients with coronary
artery disease. MPs of diabetic retinopathy and diabetic foot ulcer patients induced
branched tube networks that were unstable and collapsed over time. This study demonstrates
that MP characteristics are related to the specific type of vascular complications
and may serve as a bio-marker for the procoagulant state and vascular pathology in
patients with T2DM.
keywords
Tissue factor/factor VII - tissue factor pathway inhibitor (TFPI) - diabetes mellitus
- endothelial cells - microparticles
