Involvement of microparticles in diabetic vascular complications

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

Research output: Contribution to journalArticlepeer-review

Abstract

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 pa- tients 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.

Original languageEnglish
Pages (from-to)310-321
Number of pages12
JournalThrombosis and Haemostasis
Volume106
Issue number2
DOIs
StatePublished - 2011
Externally publishedYes

Keywords

  • Diabetes mellitus
  • Endothelial cells
  • Microparticles
  • Tissue factor / factor VII
  • Tissue factor pathway inhibitor (TFPI)

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