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

Juan Liu,Haitao Zeng,Xiangbin Xing,Xiang Li,Xinlin Wu,Zi Ren,Shaohong Wu,Shun Yao

doi:10.1155/2020/1278465

Abstract

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.

Highlights

In the last decade, type 2 diabetes mellitus (T2DM) is regarded as one of the most popular metabolic diseases in China, which leads to an increased risk of diabetes-related morbidity or mortality due to its concomitant macrovascular and microvascular complications [1]
No study has been reported relating to the underlying mechanism of why the inability of circulating endothelial progenitor cells’ (EPCs) is present in prediabetic individuals. e question of whether or not there is a difference in the inability of circulating EPCs between impaired glucose tolerance (i-IGT) and impaired fasting glucose (i-IFG) subjects is still left behind since the two different prediabetic status are regarded as having different pathophysiological characteristics
The following issues still need further investigation: (1) if the inability of circulating EPCs is present in premenopausal i-IGT or i-IFG women? (2) If that is, what is the possible underlying mechanism? Whether or not nitric oxide (NO) production will be responsible for the deleterious changes of circulating EPCs in the targeted population just as it was in diabetic and hypertensive patients? Attempting to elucidate the abovementioned questions, the present study evaluated circulating EPCs’ number and function, endothelial function in premenopausal normal glucose tolerance (NGT), i-IFG, or i-IGT women

Summary

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. 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). 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. E expression of GTCPH I as well as intracellular BH4 levels declined in i-IGT women; the alternations of key proteins’ expression in the Tie2/Akt/eNOS signaling pathway were not observed in either i-IGT or i-IFG women. E endothelial repair capacity was impaired in i-IGT premenopausal women but was preserved in i-IFG counterparts. Conclusions. e endothelial repair capacity was impaired in i-IGT premenopausal women but was preserved in i-IFG counterparts. e underlying mechanism may be associated with the downregulated GTCPH I pathway and reduced NO productions

Introduction

Materials and Methods

Results