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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

Gala Tsimerman
1   Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel
,
Ariel Roguin
1   Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel
3   Interventional Cardiology Unit, Rambam Health Care Campus, Haifa, Israel
,
Anat Bachar
4   Ophthalmology Department, Rambam Health Care Campus, Haifa, Israel
,
Eyal Melamed
5   Orthopedics Department, Rambam Health Care Campus, Haifa, Israel
,
Benjamin Brenner
1   Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel
2   Thrombosis and Hemostasis Unit, Rambam Health Care Campus, Haifa, Israel
,
Anat Aharon
1   Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel
2   Thrombosis and Hemostasis Unit, Rambam Health Care Campus, Haifa, Israel
› Author Affiliations Financial support: This study was supported by grant of the Israel Ministry of Justice (3–6566) and Ministry of Health, Chief Scientist Office (3–6032).
Further Information

Publication History

Received: 14 November 2010

Accepted after major revision: 16 May 2011

Publication Date:
25 November 2017 (online)

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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
 

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