Endothelial colony-forming cells: Biological and functional abnormalities in patients with recurrent, unprovoked venous thromboembolic disease

Thromb Res. 2016 Jan:137:157-168. doi: 10.1016/j.thromres.2015.11.005. Epub 2015 Nov 10.

Abstract

Introduction: Endothelial cells (ECs) are an important component of the blood coagulation system because it maintains blood fluid. Because in patients with venous thromboembolic disease (VTD) a thrombophilic condition is not found sometimes, we investigated if endothelial colony-forming cells (ECFCs) from these patients have biological and functional abnormalities.

Patients and methods: Human mononuclear cells (MNCs) were obtained from peripheral blood from patients with VTD and controls to obtain ECFCs. These cells were assayed for their immunophenotype and electron microscopy characteristics and their ability to form capillary-like structures and to produce pro-inflammatory and pro-angiogenic cytokines and reactive oxygen species (ROS).

Results: ECFCs appeared at 7 and 21 days of culture in VTD patients and controls, respectively. ECFCs increased 8-fold in patients and emerged 1 week earlier. No differences in the size of the colonies of ECFCs were found. Numbers and time of appearance of ECFCs was different between groups. ECFC-derived ECs (ECFC-ECs) of both groups expressed CD31, CD34, CD146, and CD-309 but none expressed CD45, CD14, or CD90. Interest CD34 was highly expressed in ECFC-ECs from patients. In both groups, ECFC-ECs showed similar capacity to form capillary-like structures but ECFC-ECs from patients had significant abnormalities in the mitochondrial membrane. We found a significant increase in ROS production in ECFC-ECs from patients. There were significant differences in cytokine profiles between VTD patients and controls.

Conclusions: We found a dysfunctional state in ECFC from VTD patients resembling some characteristics of dysfunctional ECs. These findings may help to understand some pathophysiological aspects of VTD.

Keywords: Deep vein thrombosis; Endothelial cells; Endothelial colony-forming cells; Thrombosis; Venous thromboembolic disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cells, Cultured
  • Cytokines / metabolism*
  • Endothelial Progenitor Cells / metabolism*
  • Endothelial Progenitor Cells / pathology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Reactive Oxygen Species / metabolism*
  • Recurrence
  • Venous Thromboembolism / metabolism*
  • Venous Thromboembolism / pathology*
  • Young Adult

Substances

  • Cytokines
  • Reactive Oxygen Species