Preventive cardiology
Circulating Levels of Endothelial Progenitor Cell Mobilizing Factors in the Metabolic Syndrome

https://doi.org/10.1016/j.amjcard.2010.07.039Get rights and content

Endothelial progenitor cells (EPCs) are an emerging biomarker of vascular health. However, there are few data on the biology and mobilizing factors of EPCs in metabolic syndrome (MS). The aim of this study was to assay EPC mobilizing factors, including granulocyte colony-stimulating factor, stem cell factor/c-kit ligand (SCF), vascular endothelial growth factor, and stromal cell–derived factor–1 levels, in patients with MS (n = 36) and age- and gender-matched controls (n = 38). There was a significant reduction of 83% in granulocyte colony-stimulating factor levels in patients with MS. Also, there were decreases in SCF and SCF soluble receptor levels. However, there was no significant difference in stromal cell–derived factor–1 levels, and paradoxically, vascular endothelial growth factor levels were increased, consistent with resistance. In conclusion, in addition to progenitor cell exhaustion as a mechanism for the decrease in EPCs in patients with MS, they also have a mobilization defect, as manifested by decreased levels of granulocyte colony-stimulating factor and SCF, resulting in a decrease in EPCs.

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Methods

All subjects were recruited from Sacramento County through fliers and advertisements in the newspaper. Subjects (aged 21 to 70 years) with MS (n = 36) and healthy controls (n = 38) were studied. MS was defined using the criteria of the National Cholesterol Education Program Adult Treatment Panel III.10 Control subjects needed to have ≤2 features of MS and not be taking blood pressure medications. Other selection criteria have been published previously.8 None of the subjects had diabetes or

Results

The 2 groups were matched for age and gender. All metabolic features, including homeostasis model assessment and high-sensitivity C-reactive protein, were significantly increased in patients with MS, and high-density lipoprotein cholesterol levels were significantly decreased (Table 1). Also, levels of PCs and EPCs were significantly decreased in patients with MS (p <0.05).

With respect to the mobilizing factors, the most significant difference was seen with granulocyte colony-stimulating factor

Discussion

We and others have previously shown that PCs and EPCs are decreased in patients with MS.6, 7, 8, 9 This finding was further confirmed in this study with a smaller sample size. This observation might have profound implications in terms of cardiovascular risk, because CD34+ cells12 and CD34+ and kinase insert domain receptor–positive cells4, 5 predict incident cardiovascular events and regulate cardiovascular homeostasis. However, the causes of PC and EPC pauperization in MS remain unclear.

Acknowledgment

We would like to thank Manpreet Kaur, University of California Davis Medical Center, for manuscript preparation.

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Dr. Jialal was supported by grant K-24 AT00596 from the National Institutes of Health, Bethesda, Maryland, and by a grant from the American Diabetes Association, Alexandria, Virginia.

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