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 ◽  
...  

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.

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Shaohong Wu ◽  
Hao He ◽  
Ge-Xiu Liu ◽  
Xiao-Peng Li ◽  
Shun Yao ◽  
...  

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.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Ibhar Al Mheid ◽  
Konstantinos Aznaouridis ◽  
Riyaz Patel ◽  
Farheen Shirazi ◽  
Diane J Sutcliffe ◽  
...  

Background: Endothelial Progenitor Cells (EPCs) are mobilized in response to endothelial injury and their counts correlate with endothelial function and cardiovascular risk burden. This rare cell population can be characterized by either flow cytometric analysis or mononuclear cell culture and colony counting, however, the 24-hour circadian variation and inter-relation of EPC measures with endothelial function remain unknown. We hypothesized that EPC levels and endothelial function will have a similar circadian variation. Methods: In 12 healthy subjects (8 men, 42 ± 18 yrs), we investigated the circadian variation of: 1-circulating cells positive for: CD34, CD133 andCD34, the number of colonies formed by culturing mononuclear cells utilizing a 7-day assay and flow-mediated vasodilation utilizing brachial artery reactivity at 8am, noon, 4pm, 8pm, midnight, 4am and 8am. Results: ANOVA for repeated measures over 24 hours indicated significant changes in the number of colony counts (p < .001, highest at midnight). Similarly, flow-mediated vasodilation was highest at midnight (p < .001). In contrast, CD34+ and dual positive CD34+ /CD133+ cell counts peaked a little earlier at 8 pm (8 pm vs.8 am p = .07 and .01 for paired t-tests, respectively). (Figure ) Conclusion: Endothelial function and EPCs estimated as colony forming units peak at midnight and are lower at other times of the day. The highest counts of circulating progenitors are seen at 8pm. There is a parallel change in circulating EPCs and vascular endothelial function during a 24-hour period, with lower levels in the morning hours.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Long Peng ◽  
Qianlin Gu ◽  
Zhenhua Huang ◽  
Lijin Zeng ◽  
Chang Chu ◽  
...  

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.


2009 ◽  
Vol 30 (5) ◽  
pp. 542-542
Author(s):  
Kathleen M. Gavin ◽  
Douglas R. Seals ◽  
Annemarie E. Silver ◽  
Kerrie L. Moreau

ABSTRACT Context and Objective Estrogen receptor α (ERα), a potent transcription factor expressed in vascular endothelial cells, plays a key role in regulating vascular function and health. We determined whether vascular endothelial cell expression of ERα is influenced by estrogen status and is related to vascular endothelial function in healthy women. Methods ERα protein expression was measured (quantitative immunofluorescence) in endothelial cells from peripheral veins of 16 healthy, premenopausal women during the early follicular (EF) and late follicular (LF) phases of the menstrual cycle and 17 estrogen-deficient postmenopausal women. Endothelial-dependent dilation (EDD; brachial artery flow-mediated dilation) and endothelial nitric oxide synthase (eNOS) expression and activation were also measured in a subgroup of women. Results In premenopausal women (n = 10), ERα expression was 30% lower (P &lt; 0.001) during the EF (low estrogen) compared with the LF (high estrogen) phase of the menstrual cycle. In postmenopausal women, ERα expression was 33% lower (P &lt; 0.001) compared with the LF phase of the menstrual cycle in premenopausal women. ERα expression was strongly related (r = 0.67; P &lt; 0.001) to EDD, which was reduced in postmenopausal women. ERα abundance was positively related to expression of eNOS (r = 0.54; P = 0.009; n = 21) and ser1177 phosphorylated eNOS (r = 0.59; P = 0.006; n = 20). Conclusions These results provide the first evidence that expression of ERα in vascular endothelial cells is modulated by estrogen status and may be a key determinant of vascular endothelial function in healthy pre- and postmenopausal women. ERα expression may influence vascular endothelial function in women by affecting protein levels and activation of eNOS.


Maturitas ◽  
2012 ◽  
Vol 71 ◽  
pp. S77
Author(s):  
M. Bracaglia ◽  
F. Ianniello ◽  
L. Quagliozzi ◽  
L. Donati ◽  
F. Basile ◽  
...  

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Kourek ◽  
K Psarra ◽  
M Alshamari ◽  
D Delis ◽  
G Mitsiou ◽  
...  

Abstract Background Vascular endothelial dysfunction is an underlying pathophysiological feature of chronic heart failure (CHF). Endothelial progenitor cells (EPCs) are being used as an index of vascular endothelial function. Cardiac rehabilitation (CR) programs have been shown to stimulate the mobilization of EPCs in CHF patients. However, the effect of different exercise training programs on the EPCs in CHF patients has not been investigated. Purpose The purpose of the study was to assess the effect of 2 different exercise training programs on the mobilization of EPCs in patients with CHF and investigate if there were differences between them. Methods Forty-four consecutive patients (35 males) with stable CHF [mean±SD, Age (years): 56±10, EF (%): 33±8, Peak VO2 (ml/kg/min): 18.4±4.4] enrolled a 36-session CR program and they were randomized in one exercise training protocol; either high-intensity interval training (HIIT) or HIIT combined with muscle strength (COM). Venous blood was drawn at rest before and after the CR program. Five circulating endothelial populations were identified and quantified by flow cytometry (Table 1). EPCs values are expressed as cells/million enucleated cells in medians (25th-75th percentiles). Results In both HIIT and COM groups, the mobilization of all circulating endothelial populations increased after the CR program (p&lt;0.05, Table 1). However, there was no difference in the mobilization of EPCs between HIIT and COM groups (p&gt;0.05, Table 1). Conclusion A 36-session cardiac rehabilitation program increases the mobilization of endothelial progenitor cells in patients with chronic heart failure. High-intensity interval exercise training and HIIT combined with muscle strength have similar beneficial effect on endothelial progenitor cells, and therefore on vascular endothelial function. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): Co-financed by Greece and the European Union (European Social Fund- ESF) through the Operational Programme “Human Resources Development, Education and Lifelong Learning” in the context of the project


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