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

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.

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

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.

scholarly journals Downregulated GTCPH I/BH4 Pathway and Decreased Function of Circulating Endothelial Progenitor Cells and Their Relationship with Endothelial Dysfunction in Overweight Postmenopausal Women

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Ying Luo ◽  
Zhenhua Huang ◽  
Jinli Liao ◽  
Zhihao Liu ◽  
Xiaopeng Li ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Postmenopausal Women ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Premenopausal Women ◽  
Endothelial Damage ◽  
Normal Weight ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Endothelial Progenitor

Endothelial progenitor cells (EPCs) have endogenous endothelium-reparative potential, but obesity impairs EPCs. Overweight premenopausal women have a normal number of circulating EPCs with functional activity, but whether EPCs in overweight postmenopausal women can repair obesity-related endothelial damage requires further investigation. For this purpose, we examined the function and number of circulating EPCs, evaluated vascular endothelial function, and explored the underlying mechanism. Compared with normal weight or overweight age-matched men, postmenopausal women (overweight or normal weight) had a diminished number of circulating EPCs and impaired vascular endothelial function, as detected by flow-mediated dilatation. Moreover, GTCPH I expression and the nitric oxide level in overweight postmenopausal women and men were significantly decreased. Together, our findings demonstrate that the number or function of circulating EPCs and endothelial function, which is partially regulated by the GTCPH I/BH4 signaling pathway, is not preserved in overweight postmenopausal women. The GTCPH I/BH4 pathway in circulating EPCs may be a potential therapeutic target for endothelial injury in overweight postmenopausal women.

scholarly journals Decreased Count and Dysfunction of Circulating EPCs in Postmenopausal Hypercholesterolemic Females via Reducing NO Production

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Ying Luo ◽  
Quan-Neng Yan ◽  
Wan-Zhou Wu ◽  
Fan-Yan Luo
Keyword(s):  
Endothelial Dysfunction ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Therapeutic Strategy ◽  
No Production ◽  
Endothelial Progenitor ◽  
Endothelial Repair ◽  
Flow Mediated Dilatation ◽  
Premenopausal Female ◽  
And Function

Endothelial progenitor cells (EPCs) contribute to the endogenous endothelial repair program during hypercholesterolemia. EPC count and migratory and proliferative capacities remain unchanged in the premenopausal female with hypercholesterolemia. However, the changes of count and activity of circulating EPCs in the hypercholesterolemic postmenopausal females are unknown. Here, we find that the migratory and proliferative capacities of circulating EPCs were decreased in patients with hypercholesterolemia versus normocholesterolemia. No significant differences were found between postmenopausal females and age-matched males. NO production showed positive correlation with the activity and count of circulating EPCs in patients with hypercholesterolemia. Flow-mediated dilatation (FMD) is directly interrelated with EPC counts and function. Our findings reveal that decreased EPC count and endothelial dysfunction lead to less NO production in hypercholesterolemic postmenopausal females. Maintaining the EPC numbers and activity might be emerging as a potential therapeutic strategy to reduce the risk of cardiovascular injury in elder women.

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

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Juan Liu ◽  
Xiangbin Xing ◽  
Xinlin Wu ◽  
Xiang Li ◽  
Shun Yao ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Impaired Glucose Tolerance ◽  
Progenitor Cells ◽  
Signaling Pathway ◽  
Endothelial Progenitor Cells ◽  
Premenopausal Women ◽  
Endothelial Progenitor ◽  
Repair Capacity ◽  
Circulating Endothelial Progenitor Cells ◽  
Endothelial Repair

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.

Abstract 189: Extended-Release Niacin Improves Endothelial Function, Restores Re-Endothelialization Capacity of Endothelial Progenitor Cells and Augments Vasoprotective Properties of HDL in Patients with Metabolic Syndrome

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Sajoscha A Sorrentino ◽  
Christian Besler ◽  
Ferdinand H Bahlmann ◽  
Martin Meyer ◽  
Maja Mueller ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Endothelial Cell ◽  
Endothelial Function ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Extended Release ◽  
Resonance Spectroscopy ◽  
No Production ◽  
Endothelial Progenitor

Background: High density lipoprotein (HDL)-targeted therapies are currently evaluated as a novel therapeutic strategy for cardiovascular disease. However, recent data suggest that HDL may become dysfunctional in metabolic syndrome (MetS). We therefore evaluated the effect of extended-release niacin (ERN) on endothelial function, re-endothelialization capacity of endothelial progenitor cells (EPC) and HDL quality, i.e. the capacity of HDL to stimulate endothelial nitric oxide (NO) production and reduce superoxide (O 2 .− ) production. Methods and Results: Thirty MetS patients were randomized to 3 month treatment with ERN (1500 mg/d) or placebo. Flow-dependent, endothelium-mediated vasodilation (FDD) was characterized by high-resolution ultrasound, EPCs were cultured and HDL was isolated by ultracentrifugation before and after therapy. In vivo re-endothelialization capacity of EPCs was tested by transplantation of EPCs (5x10 5 cells) into nude mice using a carotid injury model. Furthermore, the effects of HDL on endothelial cell superoxide (O 2 . − ) and NO production were determined by electron spin resonance spectroscopy. ERN therapy significantly raised HDL levels (36.4±4.2 vs. 43.4±6.9 mg/dl, P <0.01), whereas no change was observed after placebo (35.9±6.2 vs. 33.7±6.1 mg/dl, P n.s.). FDD was improved by ERN (5.2±1.8 vs 9.8±2.2%; P<0.01), but not after placebo therapy (4.9±1.5 vs. 4.3±0.9 %; P n.s.). Moreover, the re-endothelialization capacity of EPCs was markedly increased after ERN, but not after placebo (REA-ERN: 34±9%; P< 0.001 vs. placebo). Importantly, HDL isolated after ERN, but not after placebo therapy stimulated endothelial cell NO production and inhibited endothelial cell O 2 . − production, suggesting that improved vasoprotective properties of HDL contributed to beneficial effects of ERN therapy on endothelial function. Conclusions: The present study demonstrates that extended-release niacin improves endothelium-dependent vasodilation, restores re-endothelialization capacity of EPCs and importantly improves vasoprotective functions of HDL from patients with metabolic syndrome. These data suggest that extended-release niacin therapy has a beneficial effect on HDL vasoprotective qualities.

Abstract 3698: Decreased Circulating Endothelial Progenitor Cells and Endothelial Dysfunction: a Novel Mechanism of Atherogenesis in Obesity.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Paulo F Leite ◽  
Claudia R Andrade ◽  
Santa Poppe ◽  
Luiz A Cesar ◽  
Silmara Coimbra ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Multivariate Analysis ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Obese Patients ◽  
Endothelial Progenitor ◽  
Circulating Endothelial Progenitor Cells ◽  
Morbid Obese

Underlying mechanisms of endothelial dysfunction in obesity are not fully understood. Circulating Endothelial Progenitor Cells (EPCs) are known to promote endothelial repair. Our aim was to assess the number/function of EPCs in morbid obese individuals and its correlation with endothelial function and inflammatory markers. EPCs were isolated from 33 morbid obese patients (age 47±1.8 y; men=34%; BMI=49±2.1 kg/m 2 , metabolic syndrome=84%) and 20 lean controls. Peripheral blood EPC number was significantly reduced in obese patients both with flow cytometry (KDR + /CD34 + ; 0.041±0.04 vs 0.074±0.05 %events, p<0.001) and fluorescence analysis after short-term culture (49±4 vs 28±2 cells/field, p<0.001). The plasma number of primitive CD 133 + cells, and concentrations of VEGF (Elisa) and nitrogen oxides (which potentially recruit EPCs), were similar to control, suggesting that reduction of EPCs occurs distally to early cell differentiation. Importantly, C-Reactive Protein (CRP), robustly increased in obese patients (0.15±0.04 vs 1.3±0.3; p=0.003), was a strong predictor of reduced EPC number at multivariate analysis (r=0.623; p < 0.001). Likewise, the migratory response of EPCs to VEGF in vitro was significantly impaired in obese vs controls, despite similar VEGF receptor numbers. Multivariate analysis suggested potential roles of metabolic syndrome and leptin in such effect. Endothelial function at flow-mediated brachial artery reactivity was markedly reduced (by 60%) in obese patients, and had a significant inverse correlation with EPC number (r= 0.678; p< 0.001). Carotid intimal thickness was also increased in obese patients (0.68±0.02 vs 0.58±0.08; p=0.001). On the other hand, the number of circulating endothelial cells (CD31 + /CD106 + ) was similar in both groups, suggesting that apoptosis was not enhanced in the obese. These results suggest for the first time that reduced number and migratory capacity of EPCs correlate with endothelial dysfunction or increased CRP and may be a key underlying mechanism of vascular complications and atherosclerosis in obesity.

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