Backgrounds: The number and activity of circulating endothelial progenitor cells (EPCs) in prehypertension is\npreserved in premenopausal women. However, whether this favorable effect still exists in prehypertensive premenopausal\nwomen with diabetes is not clear.\nMethods: This study compared the number and functional activity of circulating EPCs in normotensive or\nprehypertensive premenopausal women without diabetes mellitus and normotensive or prehypertensive\npremenopausal women with diabetes mellitus, evaluated the vascular endothelial function in each groups,\nand investigated the possible underlying mechanism.\nResults: We found that compared with normotensive premenopausal women, the number and function of\ncirculating EPCs, as well as endothelial function evaluated by flow-mediated dilatation (FMD) in prehypertensive\npremenopausal women were preserved. In parallel, the Tie2/Akt/eNOS signaling pathway and the plasma NO level or\nNO secretion of circulating EPCs in prehypertensive premenopausal women was also retained. However, in presence\nof normotension or prehypertension with diabetes mellitus, the number or function of circulating EPCs and FMD in\npremenopausal women decreased. Similarly, the phosphorylation of Tie2/Akt/eNOS signaling pathway and the plasma\nNO level or NO secretion of circulating EPCs was reduced in prehypertension premenopausal with diabetes mellitus.\nConclusion: The present findings firstly demonstrate that the unfavorable effects of diabetes mellitus on number and\nactivity of circulating EPCs in prehypertension premenopausal women, which is at least partially related to the\nabnormal phosphorylation of Tie2/Akt/eNOS signaling pathway and subsequently reduced nitric oxide bioavailability. The\nTie2/Akt/eNOS signaling pathway may be a potential target of vascular protection in prehypertensive premenopausal\nwomen with diabetes mellitus
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