Endothelial Nitric Oxide Synthase as A Marker for Human Endothelial Progenitor Cells

Qiao, Wei; Niu, Lingying; Zhao, Lijun; Qiao, Tiankui; Liu, Changjian

doi:10.1620/tjem.221.19

Cited by 23 publications

(19 citation statements)

References 34 publications

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“…Moreover, it has been described that NO and eNOS participates in the neovascularization process via mobilization of progenitor cells from brown marrow stem cell niches to the peripheral circulation. 17 Interestingly, eNOS activity has been described in progenitor endothelial cells, 18,19 and eNOS expression is required for mobilizing EPC from bone marrow toward the circulation. 20 Due to the dependence of L-arginine transport for NO synthesis in differentiate endothelium, we wonder whether this mechanism is present in hEPC.…”

Section: Introductionmentioning

confidence: 99%

L-Arginine Transport and Nitric Oxide Synthesis in Human Endothelial Progenitor Cells

Díaz-Pérez

Radojkovic

Aguilera

et al. 2012

Journal of Cardiovascular Pharmacology

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Nitric oxide (NO) is an endogenous vasodilator molecule synthetized from L-arginine by a family of nitric oxide synthases. In differentiated human endothelial cells, it is well known that L-arginine uptake via cationic amino acid transporters (y(+)/CAT) or system y(+)L is required for the NO synthesis via endothelial nitric oxide synthase, but there are no reports in human endothelial progenitor cell (hEPC). Therefore, we isolated hEPCs from peripheral blood of healthy donors and cultured them for either 3 (hEPC-3d) or 14 days (hEPC-14d) to characterize the L-arginine transport and NO synthesis in those cells. L-arginine transport and NO synthesis were analyzed in the presence or absence of N-ethylmaleimide or L-nitroarginine methyl ester, as inhibitors of y(+)/CAT system and nitric oxide synthases, respectively. The results showed that L-arginine uptake is higher in hEPC-14d than in hEPC-3d. Kinetic parameters for L-arginine transport showed the existence of at least 2 transporter systems in hEPC: a high affinity transporter system (K(m)= 4.8 ± 1.1 μM for hEPC-3d and 6.1 ± 2.4 μM for hEPC-14d) and a medium affinity transporter system (K(m) = 85.1 ± 4.0 μM for hEPC-3d and 95.1 ± 8 μM for hEPC-14d). Accordingly, hEPC expressed mRNA and protein for CAT-1 (ie, system y(+)) and mRNA for 2 subunits of y(+)L system, yLAT1, and 4F2hc. Higher L-citruline production and NO bioavailability (4-fold), and endothelial nitric oxide synthase expression (both mRNA and protein) were observed in hEPC-14d compared with hEPC-3d. Finally, the high L-citruline formation observed in hEPC-14d was blocked by N-ethylmaleimide. In conclusion, this study allowed to identity a functional L-arginine/NO pathway in two hEPC differentiation stages, which improves the understanding of the physiology of these precursor cells.

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Section: Introductionmentioning

confidence: 99%

L-Arginine Transport and Nitric Oxide Synthesis in Human Endothelial Progenitor Cells

Díaz-Pérez

Radojkovic

Aguilera

et al. 2012

Journal of Cardiovascular Pharmacology

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“…In addition to endothelial cells, eNOS is present on circulating blood cells, including circulating angiogenic MNCs, and on circulating microparticles, therefore its regulation impacts on the overall homeostasis of the vascular tree controlling blood flow restoration via angiogenesis, vasculogenesis, and arteriogenesis (23)(24)(25)(26). Together with neuronal NOS (nNOS), eNOS is constitutively expressed.…”

Section: The Enos Signaling Pathway and The Control Of Angiogenesismentioning

confidence: 99%

The genetics of exceptional longevity identifies new druggable targets for vascular protection and repair

Puca

Spinetti

Vono

et al. 2016

Pharmacological Research

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms AbstractTherapeutic angiogenesis is a relatively new medical strategy in the field of cardiovascular diseases.The underpinning concept is that angiogenic growth factors or proangiogenic cells could be exploited therapeutically in cardiovascular patients to enhance native revascularization responses to an ischemic insult, thereby accelerating tissue healing. The initial enthusiasm generated by preclinical studies has been tempered by the modest success of clinical trials assessing therapeutic angiogenesis. Similarly, proangiogenic cell therapy has so far not maintained the original promises.Intriguingly, the current trend is to consider regeneration as a prerogative of the youngest organism.Consequentially, the embryonic and foetal models are attracting much attention for clinical translation into corrective modalities in the adulthood. Scientists seem to undervalue the lesson from Mother Nature, e.g. all humans are born young but very few achieve the goal of an exceptional healthy longevity. Either natural experimentation is driven by a supreme intelligence or stochastic phenomena, one has to accept the evidence that healthy longevity is the fruit of an evolutionary process lasting million years. It is therefore extremely likely that results of this natural experimentation are more reliable and translatable than the intensive, but very short human investigation on mechanisms governing repair and regeneration. With this preamble in mind, here we propose to shift the focus from the very beginning to the very end of human life and thus capture the secret of prolonged health span to improve well-being in the adulthood.

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“…The possible mechanisms include decreasing of NO generation [20] and apoptosis induced by MAPKs pathways [21]. eNOS regulates the generation of NO and acts as a bio-marker of EOCs for cell identification [22]. On the other hand, ADMA inhibits the synthesis of NO and O 2 − and then hinders the cellular damage caused by NMDA [23].…”

Section: Discussionmentioning

confidence: 99%

Regulation of c-Jun N-Terminal Protein Kinase (JNK) Pathway in Apoptosis of Endothelial Outgrowth Cells Induced by Asymmetric Dimethylarginine

et al. 2017

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BackgroundEndothelial outgrowth cells (EOCs) are terminal endothelial progenitor cells (EPCs). Asymmetric dimethylarginine (ADMA) has been identified as a novel risk factor for cardiovascular diseases. Our aim in the present study was to investigate the effect of regulation of asymmetric dimethylarginine (ADMA) on EOCs apoptosis and to explore the underlining mechanisms of c-Jun N-terminal protein kinase (JNK) pathway in the process.Material/MethodsEOCs were harvested from umbilical cord blood and obtained by using density gradient centrifugation and adhesive culture methods. Endothelial characteristics were identified by immunohistochemistry and fluorescence staining. EOCs were treated with different concentrations of ADMA and detected by flow cytometry. After JNK specific inhibitor (SP600125) was added, EOCs apoptosis protein expressions were measured by Western blot analysis. Proliferation, migration, and vascularization were detected by CCK-8 assay, wound healing assay, and tube-like formation assay, respectively.ResultsEOCs were successfully extracted from umbilical cord blood and different concentrations of ADMA aggravated EOCs apoptosis. ADMA distinctly activates the phosphorylation activity of JNK. Supplementation of JNK-specific inhibitor (SP600125) decreased expression of Bax and cleaved caspase 3/9, and alleviated ADMA-induced apoptosis. SP600125 also promoted angiogenesis viability.ConclusionThe JNK pathway participates in the apoptosis-promoting process of EOCs, and targeted inhibition of the JNK pathway can alleviate ADMA-induced injury, which Is the potential underlying mechanism of vascular endothelium injury in ischemic stroke.

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Endothelial Nitric Oxide Synthase as A Marker for Human Endothelial Progenitor Cells

Cited by 23 publications

References 34 publications

L-Arginine Transport and Nitric Oxide Synthesis in Human Endothelial Progenitor Cells

L-Arginine Transport and Nitric Oxide Synthesis in Human Endothelial Progenitor Cells

The genetics of exceptional longevity identifies new druggable targets for vascular protection and repair

Regulation of c-Jun N-Terminal Protein Kinase (JNK) Pathway in Apoptosis of Endothelial Outgrowth Cells Induced by Asymmetric Dimethylarginine

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