Decreased number and impaired functionality of endothelial progenitor cells in subjects with metabolic syndrome: implications for increased cardiovascular risk

Abstract

Objective: Metabolic syndrome (MetS) is characterized by low-grade inflammation and confers an increased risk for cardiovascular disease. Endothelial progenitor cells (EPCs) are a measure of vascular health and are decreased in patients with various risk factors for cardiovascular disease (CVD). There is a paucity of data examining the EPC status especially in terms of their functionality in MetS subjects without diabetes or cardiovascular disease. We aimed to enumerate and functionally characterize EPCs in subjects with MetS in comparison to healthy controls.

Methods: The study was performed at the University of California Davis Medical Center. Healthy controls (n=31) and MetS (n=46) subjects were included in the study. EPCs were enumerated in fasting blood by KDR/CD34 dual positivity. Functionality was assessed by the colony forming units (CFU) assay, migration and tubule formation.

Results: Subjects with MetS had significantly decreased number of EPCs compared to control subjects. Furthermore, EPCs from MetS subjects depicted significantly impaired clonogenic capacity, i.e., decreased colony forming units, and impaired capacity to incorporate into tubular structures suggesting functional impairment of EPCs from MetS subjects.

Conclusions: We make the novel observation that MetS subjects without diabetes or CVD have decreased EPC number and impaired functionality as compared to control subjects. These findings could contribute to the increased CV risk in this population.

Conflict of interest statement

None of the authors report any conflicts of interest.

Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Figures

Fig 1

Enumeration of EPCs by FACS. CD34/KDR dual positive cells in all the subjects were assessed as described in Methods. * p

Fig 2

Fig 2a: CFU in control and MetS subjects. Number of CFUs were ennumerated as described in Methods * p<0.001 compared to control EPCs Fig 2b: Migration assay in control and MetS subjects. A Boyden chamber assay was used with growth factor-free medium or VEGF (100 ng/ml) supplemented medium. Fig 2c: Vasculogenic capacity of EPCs (DiI-labeled) as measured by their incorporation into tubules formed by HAEC on matrigel. Fluorescence and phase contrast images are shown in the figure. Significantly fewer EPCs from MetS subjects were incorporated into the tubules formed by HAEC than those of the normal controls. EPCs incorporation in the MetS group was reduced by 33%. *P<0.05.

Fig 2

Fig 2a: CFU in control and MetS subjects. Number of CFUs were ennumerated as described in Methods * p<0.001 compared to control EPCs Fig 2b: Migration assay in control and MetS subjects. A Boyden chamber assay was used with growth factor-free medium or VEGF (100 ng/ml) supplemented medium. Fig 2c: Vasculogenic capacity of EPCs (DiI-labeled) as measured by their incorporation into tubules formed by HAEC on matrigel. Fluorescence and phase contrast images are shown in the figure. Significantly fewer EPCs from MetS subjects were incorporated into the tubules formed by HAEC than those of the normal controls. EPCs incorporation in the MetS group was reduced by 33%. *P<0.05.

Fig 2

Fig 2a: CFU in control and MetS subjects. Number of CFUs were ennumerated as described in Methods * p<0.001 compared to control EPCs Fig 2b: Migration assay in control and MetS subjects. A Boyden chamber assay was used with growth factor-free medium or VEGF (100 ng/ml) supplemented medium. Fig 2c: Vasculogenic capacity of EPCs (DiI-labeled) as measured by their incorporation into tubules formed by HAEC on matrigel. Fluorescence and phase contrast images are shown in the figure. Significantly fewer EPCs from MetS subjects were incorporated into the tubules formed by HAEC than those of the normal controls. EPCs incorporation in the MetS group was reduced by 33%. *P<0.05.