Effects of Fluid Shear Stress on eNOS mRNA Expression and NO Production in Human Endothelial Progenitor Cells

SummaryShear stress has an established effect on mature endothelial cells, but less is known about how shear stress regulates endothelial progenitor cells (EPCs). In vitro expanded EPCs isolated from adult human blood represent a novel tool in regenerative vessel therapy. However, in vitro culturing may generate cells with unfavourable properties. The aim of the present study was therefore to assess whether shear stress may influence the inflammatory and thrombotic phenotype of in vitro expanded EPCs. In late outgrowth EPCs, 6 hours of shear stress (6.0 dynes/ cm2) significantly reduced the mRNA levels of IL-8, COX2, and tissue factor (TF) compared to static controls. This was associated with a reduced TF activity. In contrast, mRNA expression of NOS3 was significantly increased following 6 and 24 hours of shear stress. In accordance with this, NOS3 protein expression was increased following 24 hours of shear stress. Overall stimulation with the proinflammatory mediator, TNFα, for the final 2 hours increased the mRNA expression of IL-6, IL-8, MCP-1, ICAM1, and TF. However exposure to 6 hours of shear stress significantly suppressed the inductory potential of TNFα to increase the mRNA levels of IL-6, IL-8, COX2, and TF. Additionally, TNFα increased TF activity approximately 10 times, an effect that was also significantly reduced by exposure to 6 and 24 hours of shear stress. The effect of shear on the gene levels of TF and NOS3 were not blocked by the NOS inhibitor L-NAME. These observations suggest that EPCs are capable of functionally responding to shear stress.

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Shear stress increases Cu/Zn SOD activity and mRNA expression in human endothelial progenitor cells

Journal of Human Hypertension ◽

10.1038/sj.jhh.1002147 ◽

2007 ◽

Vol 21 (5) ◽

pp. 353-358 ◽

Cited By ~ 32

Author(s):

J Tao ◽

Z Yang ◽

J-Mei Wang ◽

L-Chun Wang ◽

C-F Luo ◽

...

Keyword(s):

Shear Stress ◽

Mrna Expression ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Endothelial Progenitor ◽

Sod Activity

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Shear stress contributes to t-PA mRNA expression in human endothelial progenitor cells and nonthrombogenic potential of small diameter artificial vessels

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2006.01.172 ◽

2006 ◽

Vol 342 (2) ◽

pp. 577-584 ◽

Cited By ~ 43

Author(s):

Zhen Yang ◽

Jun Tao ◽

Jie-Mei Wang ◽

Chang Tu ◽

Ming-Guo Xu ◽

...

Keyword(s):

Shear Stress ◽

Mrna Expression ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Small Diameter ◽

Endothelial Progenitor

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Shear stress induces eNOS mRNA expression and improves endothelium-dependent dilation in senescent soleus muscle feed arteries

Journal of Applied Physiology ◽

10.1152/japplphysiol.00408.2004 ◽

2005 ◽

Vol 98 (3) ◽

pp. 940-946 ◽

Cited By ~ 57

Author(s):

Christopher R. Woodman ◽

Elmer M. Price ◽

M. Harold Laughlin

Keyword(s):

Shear Stress ◽

Mrna Expression ◽

Soleus Muscle ◽

Low Flow ◽

No Production ◽

Fischer 344 ◽

Enos Mrna ◽

Series Of Experiments ◽

Endothelial Nitric Oxide ◽

Feed Arteries

We tested the hypothesis that increased intraluminal shear stress induces endothelial nitric oxide (NO) synthase (eNOS) mRNA expression and improves endothelium-dependent dilation in senescent soleus muscle feed arteries (SFA) by increasing NO production. SFA were isolated from young (4 mo) and old (24 mo) male Fischer 344 rats and cannulated with two resistance-matched glass micropipettes. SFA were exposed to no flow (NF), low flow (LF), intermediate flow (IF), or high flow (HF) for 4 h. Mean intraluminal shear stress ranged from 0 to 82 dyn/cm2. At the end of the 4-h treatment period, eNOS mRNA expression was assessed in each SFA. eNOS mRNA expression was significantly lower in old NF SFA than in young NF SFA. In old SFA, eNOS mRNA expression was induced by IF (+154%) and HF (+136%), resulting in a level of expression that was not different from that of young SFA. In a separate series of experiments, SFA were pretreated with NF or HF for 4 h, and endothelial function was assessed by examining vasodilator responses to ACh. ACh-induced dilation was less in old NF SFA than young NF SFA. Pretreatment with HF improved ACh-induced dilation in old SFA such that the response was similar to that of young SFA. In the presence of Nω-nitro-l-arginine to inhibit NOS, ACh-induced dilation was inhibited in old HF SFA such that the response was no longer greater than that of old NF SFA. These results indicate that increased intraluminal shear stress induces eNOS mRNA expression and improves endothelium-dependent dilation in senescent SFA by increasing NO production.

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

Stem Cells International ◽

10.1155/2018/2543847 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 1

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.

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β2AR-dependent signaling contributes to in-vivo reendothelialization capacity of endothelial progenitor cells by shear stress

Journal of Hypertension ◽

10.1097/hjh.0000000000002203 ◽

2020 ◽

Vol 38 (1) ◽

pp. 82-94 ◽

Cited By ~ 1

Author(s):

Qingsong Hu ◽

Tao Zhang ◽

Yan Li ◽

Jianyi Feng ◽

Ruqiong Nie ◽

...

Keyword(s):

Shear Stress ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Endothelial Progenitor

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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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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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