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

Background. Individuals at a prediabetic stage have had an augmented cardiovascular disease (CVD) risk and CVD-related mortality compared to normal glucose tolerance (NGT) individuals, which may be attributed to the impaired vascular endothelial repair capacity. In this study, circulating endothelial progenitor cells’ (EPCs) number and activity were evaluated, and the underlying mechanisms in premenopausal women with impaired glucose regulation were explored. Methods. Circulating EPCs’ number and activity and flow-mediated dilation (FMD) were compared in premenopausal women with NGT, isolated impaired fasting glucose (i-IFG), or isolated impaired glucose tolerance (i-IGT). Plasma nitric oxide (NO), EPCs-secreted NO, and intracellular BH4 levels were also measured. The key proteins (Tie2, Akt, eNOS, and GTPCH I) in the guanosine triphosphate cyclohydrolase/tetrahydrobiopterin (GTPCH/BH4) pathway and Tie2/Akt/eNOS signaling pathway were evaluated in these women. Results. It was observed that the i-IGT premenopausal women not i-IFG premenopausal women had a significant reduction in circulating EPCs’ number and activity as well as reduced FMD when compared to NGT subjects. Plasma NO levels or EPCs-secreted NO also decreased only in i-IGT women. The expression of GTCPH I as well as intracellular BH4 levels declined in i-IGT women; however, the alternations of key proteins’ expression in the Tie2/Akt/eNOS signaling pathway were not observed in either i-IGT or i-IFG women. Conclusions. The endothelial repair capacity was impaired in i-IGT premenopausal women but was preserved in i-IFG counterparts. The underlying mechanism may be associated with the downregulated GTCPH I pathway and reduced NO productions.

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Rejuvenated Circulating Endothelial Progenitor Cells and Nitric Oxide in Premenopausal Women with Hyperhomocysteinemia

Cardiology Research and Practice ◽

10.1155/2020/5010243 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Long Peng ◽

Qianlin Gu ◽

Zhenhua Huang ◽

Lijin Zeng ◽

Chang Chu ◽

...

Keyword(s):

Nitric Oxide ◽

Endothelial Function ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Premenopausal Women ◽

Underlying Mechanism ◽

No Production ◽

Endothelial Progenitor ◽

Repair Capacity ◽

Circulating Endothelial Progenitor Cells

Hyperhomocysteinemia (HHcy) induced endothelial dysfunction is associated with disturbance in circulating endothelial progenitor cells (EPCs). Nevertheless, whether this unfavorable effect of HHcy on circulating EPCs also exists in premenopausal women is still unknown. Therefore, this leaves an area for the investigation of the difference on the number and activity of circulating EPCs in premenopausal women with hyperhomocysteinemia and its underlying mechanism. The number of circulating EPCs was measured by fluorescence-activated cell sorter analysis, as well as DiI-acLDL and lectin fluorescent staining. The migration and proliferation of circulating were evaluated by the Transwell chamber assay and MTT. Additionally, the endothelial function and levels of nitric oxide (NO), VEGF, and GM-CSF in plasma and culture medium were determined. The number or activity of circulating EPCs and flow-mediated dilatation (FMD) in premenopausal women with or without HHcy were higher than those in postmenopausal women. However, no significant effect of HHcy on the number or activity of circulating EPCs in premenopausal women was observed. A similar alteration in NO level between the four groups was observed. There was a correlation between FMD and the number or activity of EPCs, as well as NO level in plasma or secretion by EPCs. For the first time, our findings illuminated the quantitive or qualitative alterations of circulating EPCs and endothelial function in premenopausal patients with HHcy are preserved, which was associated with retained NO production. The recuperated endothelial repair capacity is possibly the potential mechanism interpreting cardiovascular protection in premenopausal women with HHcy.

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Abnormal phosphorylation of Tie2/Akt/eNOS signaling pathway and decreased number or function of circulating endothelial progenitor cells in prehypertensive premenopausal women with diabetes mellitus

BMC Endocrine Disorders ◽

10.1186/s12902-016-0093-y ◽

2016 ◽

Vol 16 (1) ◽

Cited By ~ 15

Author(s):

Haitao Zeng ◽

Yanping Jiang ◽

Hailin Tang ◽

Zi Ren ◽

Gaofeng Zeng ◽

...

Keyword(s):

Diabetes Mellitus ◽

Progenitor Cells ◽

Signaling Pathway ◽

Endothelial Progenitor Cells ◽

Premenopausal Women ◽

Endothelial Progenitor ◽

Circulating Endothelial Progenitor Cells

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Impaired Endothelial Repair Capacity of Early Endothelial Progenitor Cells in Prehypertension

Hypertension ◽

10.1161/hypertensionaha.109.141614 ◽

2010 ◽

Vol 55 (6) ◽

pp. 1389-1397 ◽

Cited By ~ 133

Author(s):

Giovanna Giannotti ◽

Carola Doerries ◽

Pavani S. Mocharla ◽

Maja F. Mueller ◽

Ferdinand H. Bahlmann ◽

...

Keyword(s):

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Endothelial Progenitor ◽

Repair Capacity ◽

Endothelial Repair

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Elevated GTP Cyclohydrolase I Pathway in Endothelial Progenitor Cells of Overweight Premenopausal Women

Cardiology Research and Practice ◽

10.1155/2020/5914916 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Shaohong Wu ◽

Hao He ◽

Ge-Xiu Liu ◽

Xiao-Peng Li ◽

Shun Yao ◽

...

Keyword(s):

Endothelial Function ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Premenopausal Women ◽

Normal Weight ◽

Female Group ◽

No Production ◽

Endothelial Progenitor ◽

Endothelial Repair ◽

Significant Difference

Background/Aims. Sexual differences exist in endothelial progenitor cells (EPCs), and various cardiovascular risk factors are associated with the preservation of endothelial function in premenopausal women. However, it is unclear whether differences in endothelial function and circulating EPCs exist between overweight premenopausal women and age-matched men. Methods. We compared EPC counting and functions in normal-weight and overweight premenopausal women and men, evaluated endothelial function in each group, and detected the expression of the guanosine triphosphate cyclohydrolase I (GTPCH I) pathway. Results. The number of EPCs was lower in the male group than in the female group, regardless of normal-weight or overweight status, and there was no significant difference between the different weight groups among females or males. Endothelial function and EPC migration and proliferation were preserved in overweight premenopausal women compared with overweight men as were nitric oxide (NO) levels in plasma and secreted by EPCs. Endothelial function, the circulating EPC population, and NO levels were not different between normal-weight and overweight premenopausal women. Flow-mediated dilatation was significantly correlated with EPC function, plasma NO levels, and EPC-secreted NO. Conclusions. This investigation provides the first evidence for sex-based differences in EPC activity and endothelial function in overweight middle-aged individuals; these differences are associated with alterations in NO production and may partly occur through downregulation of the GTPCH I pathway. The present results provide new insights into the mechanism underlying the preserved endothelial function in overweight premenopausal women and may uncover a potential therapeutic target for endothelial repair in overweight population.

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