Reduced Circulating Endothelial Progenitor Cells and Downregulated GTCPH I Pathway Related to Endothelial Dysfunction in Premenopausal Women with Isolated Impaired Glucose Tolerance

Figures

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  Figure 1. Number and activity of circulating EPCs in the three groups. Circulating EPCs were evaluated by (a) flow cytometric analysis and (b) cell culture assay. The number of circulating EPCs in premenopausal women with i-IGT was significantly lower than that in NGT and i-IFG women (both P < 0.05). No difference of the number of circulating EPCs was observed between NGT and i-IFG women. The migratory (c) and proliferative (d) activities of circulating EPCs in premenopausal women i-IGT were significantly decreased compared to NGT and i-IFG women (all P < 0.05). No difference of the activity of circulating EPCs was observed between NGT and IFG women. Data are given as mean ± SD (∗P < 0.05 vs. NGT; #P < 0.05 vs. IFG, n = 20 for the NGT group and i-IGT group and n = 21 for the IFG group). NGT: normal glucose tolerance; i-IFG: isolated impaired fasting glucose; i-IGT: isolated impaired glucose tolerance; acLDL, acetylated low-density lipoprotein; CD, cluster of differentiation; KDR, kinase-insert domain receptor; EPCs, endothelial progenitor cells.

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  Figure 2. The NO, VEGF, and GM-CSF levels in plasma and secretion by EPCs in the three groups. Both the plasma NO level (a) and NO secretion by EPCs (d) in premenopausal women with i-IGT was significantly lower than NGT and i-IFG women (all P < 0.05). No difference of NO levels either in plasma or in culture media was observed between NGT and i-IFG women (a and b). No significant difference of VEGF or GM-CSF was found either in plasma level (b and c) or in secretion by EPCs (e and f) between the three groups. Data are given as mean ± SD (∗P < 0.05 vs. NGT; #P < 0.05 vs. IFG, n = 20 for the NGT group and i-IGT group and n = 21 for IFG group). NGT: normal glucose tolerance; i-IFG: isolated impaired fasting glucose; i-IGT: isolated impaired glucose tolerance; GM-CSF, granulocyte macrophage-colony stimulating factor; NGT, normal glucose tolerance; NOx, nitric oxide; VEGF, vascular endothelial growth factor.

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  Figure 3. The correlations between circulating EPCs or NO production and FMD. The number of circulating EPCs evaluated by flow cytometric analysis (a) or by cell culture (b) strongly correlated with FMD. The migratory (c) or proliferate (d) activity of circulating EPCs also correlated with FMD. Both plasma NO level (e) and NO secretion by EPCs (f) correlated with FMD. LDL, low density lipoprotein; CD, cluster of differentiation; KDR, kinase-insert domain receptor; FMD, flow-mediated brachial artery dilatation; EPCs, endothelial progenitor cells; NO, nitric oxide.

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  Figure 4. The CTCPH I/BH4 pathway and the Tie2/Akt/eNOS signaling pathway of circulating EPCs in the three groups. Both GTCPH I expression (a) and intracellular BH4 (b) levels were lower in premenopausal women with i-IGT than that in NGT and IFG women (all P < 0.05). No difference of the two indexes was observed between NGT and i-IFG women. Either the phosphorylation forms or the total protein of tie2 (c), Akt (d), and eNOS (e) of circulating EPCs had not exhibited significant difference between each two groups. Data are given as mean ± SD (∗P < 0.05 vs. NGT; #P < 0.05 vs. IFG, n = 20 for the NGT group and i-IGT group and n = 21 for IFG group). NGT: normal glucose tolerance; i-IFG: isolated impaired fasting glucose; i-IGT: isolated impaired glucose tolerance; GTPCH: guanosine triphosphate cyclohydrolase; BH4: tetrahydrobiopterin; Tie2: tyrosine kinase with immunoglobulin and epidermal growth factor homology domain-2; Akt: protein kinase B; eNOS: endothelial nitric oxide synthase.