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Reduced proliferation of endothelial colony-forming cells in unprovoked venous thromboembolic disease as a consequence of endothelial dysfunction
- Source :
- PLoS ONE, Vol 12, Iss 9, p e0183827 (2017), PLoS ONE
- Publication Year :
- 2017
- Publisher :
- Public Library of Science (PLoS), 2017.
-
Abstract
- Background Venous thromboembolic disease (VTD) is a public health problem. We recently reported that endothelial colony-forming cells (ECFCs) derived from endothelial cells (EC) (ECFC-ECs) from patients with VTD have a dysfunctional state. For this study, we proposed that a dysfunctional status of these cells generates a reduction of its proliferative ability, which is also associated with senescence and reactive oxygen species (ROS). Methods and results Human mononuclear cells (MNCs) were obtained from peripheral blood from 40 healthy human volunteers (controls) and 50 patients with VTD matched by age (20-50 years) and sex to obtain ECFCs. We assayed their proliferative ability with plasma of patients and controls and supernatants of cultures from ECFC-ECs, senescence-associated β-galactosidase (SA-β-gal), ROS, and expression of ephrin-B2/Eph-B4 receptor. Compared with cells from controls, cells from VTD patients showed an 8-fold increase of ECFCs that emerged 1 week earlier, reduced proliferation at long term (39%) and, in passages 4 and 10, a highly senescent rate (30±1.05% vs. 91.3±15.07%, respectively) with an increase of ROS and impaired expression of ephrin-B2/Eph-4 genes. Proliferation potential of cells from VTD patients was reduced in endothelial medium [1.4±0.22 doubling population (DP)], control plasma (1.18±0.31 DP), or plasma from VTD patients (1.65±0.27 DP). Conclusions As compared with controls, ECFC-ECs from individuals with VTD have higher oxidative stress, proliferation stress, cellular senescence, and low proliferative potential. These findings suggest that patients with a history of VTD are ECFC-ECs dysfunctional that could be associated to permanent risk for new thrombotic events.
- Subjects :
- Male
0301 basic medicine
Physiology
Cardiovascular Procedures
Cellular differentiation
lcsh:Medicine
Apoptosis
030204 cardiovascular system & hematology
medicine.disease_cause
Vascular Medicine
Biochemistry
Spectrum Analysis Techniques
0302 clinical medicine
Medicine and Health Sciences
Endothelial dysfunction
Receptor
lcsh:Science
Energy-Producing Organelles
Cells, Cultured
Cellular Senescence
Venous Thrombosis
Fluorescence-Activated Cell Sorting
education.field_of_study
Multidisciplinary
Cell Death
Stem Cells
Receptor, EphA4
Cell Differentiation
Venous Thromboembolism
Middle Aged
Body Fluids
Mitochondria
Deep Vein Thrombosis
Blood
Cell Processes
Spectrophotometry
Cardiology
Female
Cytophotometry
Anatomy
Cellular Structures and Organelles
Research Article
Adult
Senescence
medicine.medical_specialty
Population
Surgical and Invasive Medical Procedures
Ephrin-B2
Bioenergetics
Research and Analysis Methods
Peripheral blood mononuclear cell
Blood Plasma
Young Adult
03 medical and health sciences
Thromboembolism
Internal medicine
medicine
Humans
education
Cell Proliferation
Cell growth
business.industry
Revascularization
lcsh:R
Biology and Life Sciences
Endothelial Cells
Cell Biology
medicine.disease
Oxidative Stress
030104 developmental biology
Endocrinology
Gene Expression Regulation
lcsh:Q
Reactive Oxygen Species
business
Oxidative stress
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 12
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....e1e9d56f29351825b83adba027845c3e