Involvement of microparticles in diabetic vascular complications

Gala Tsimerman; Ariel Roguin; Anat Bachar; Eyal Melamed; Benjamin Brenner; Anat Aharon

doi:10.1160/TH10-11-0712

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2011; 106(02): 310-321
DOI: 10.1160/TH10-11-0712

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Involvement of microparticles in diabetic vascular complications

Authors

Gala Tsimerman

¹Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel
Ariel Roguin

¹Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel

³Interventional Cardiology Unit, Rambam Health Care Campus, Haifa, Israel
Anat Bachar

⁴Ophthalmology Department, Rambam Health Care Campus, Haifa, Israel
Eyal Melamed

⁵Orthopedics Department, Rambam Health Care Campus, Haifa, Israel
Benjamin Brenner

¹Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel

²Thrombosis and Hemostasis Unit, Rambam Health Care Campus, Haifa, Israel
Anat Aharon

¹Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel

²Thrombosis and Hemostasis Unit, Rambam Health Care Campus, Haifa, Israel

Abstract

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

Full Text

References

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