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Increased circulating endothelial progenitor cells (EPCs) in prepubertal children born prematurely: a possible link between prematurity and cardiovascular risk

Pediatric Research volume 90, pages 156–165 (2021)Cite this article

Abstract

Background

Endothelial progenitor cells (EPCs) ensure vascular integrity and neovascularization. No studies have investigated EPCs in preterm-born children beyond infancy.

Methods

One hundred and thirty-six prepubertal children were enrolled: 63 preterm and 73 born at term (controls). Circulating CD34(+)/VEGFR-2(+)/CD45(−) and CD34(+)/VEGFR-2(+)/CD45dim EPCs were measured in preterm-born children compared to controls. Body mass index (BMI), waist-to-hip ratio (WHR), neck circumference, systolic and diastolic blood pressure (SBP and DBP, respectively), fasting glucose, insulin, lipid profile, common carotid and abdominal aortic intima-media thickness (cIMT and aIMT, respectively), endothelium-dependent brachial artery flow-mediated dilation (FMD), and echocardiographic parameters were also assessed.

Results

Circulating CD34(+)/VEGFR-2(+)/CD45(−) and CD34(+)/VEGFR-2(+)/CD45dim EPCs were significantly higher in preterm-born children compared to controls (p < 0.001 and p < 0.001, respectively). In total study population and in the preterm-born group, EPCs were significantly lower in children born to mothers with gestational diabetes compared to non-diabetic mothers. Prematurity was associated with higher WHR, neck circumference, SBP, DBP, cIMT, aIMT, mean pressure, and velocity of pulmonary artery; the peak velocity of the brachial artery was significantly lower in children born prematurely. In multiple regression analysis, preterm birth and maternal gestational diabetes were recognized as independent predictors of EPCs.

Conclusions

Circulating EPCs were increased in prepubertal preterm-born children in comparison with peers born full-term. Maternal gestational diabetes was associated with a decrease in EPCs.

Impact

  • Mounting evidence supports the adverse effect of prematurity on cardiovascular health. However, the underlying mechanisms that could lead to endothelial dysfunction in preterm-born individuals are not fully understood.

  • Endothelial progenitor cells (EPCs) ensure vascular integrity, normal endothelial function and neovascularization.

  • No studies have investigated the EPCs counts in peripheral blood beyond infancy in children born prematurely.

  • Circulating EPCs were significantly higher in preterm-born prepubertal children compared to controls, thus indicating that prematurity is possibly associated with endothelial damage.

  • In total study population and in the preterm-born group, maternal gestational diabetes was associated with decreased EPCs concentrations.

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Fig. 1: Gating strategy of endothelial progenitor cells (EPCs).
Fig. 2: Representative prints out of flow cytometric determination of endothelial progenitor cells (EPCs) in preterm-born children and in children born at term.

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Acknowledgements

The authors thank the children and their parents for participating. This work was supported by National and Kapodistrian University of Athens. The funding source played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Author information

Affiliations

  1. Neonatal Unit, First Department of Pediatrics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

    Panagiota Markopoulou & Tania Siahanidou

  2. Laboratory of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

    Eleni Papanikolaou

  3. Department of Cardiology, “Agia Sofia” Children’s Hospital, Athens, Greece

    Sofia Loukopoulou

  4. Radiology Department, “Agia Sofia” Children’s Hospital, Athens, Greece

    Paraskevi Galina

  5. Unit of Clinical and Translational Research in Endocrinology, First Department of Pediatrics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece

    Aimilia Mantzou

Authors
  1. Panagiota Markopoulou
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  2. Eleni Papanikolaou
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  3. Sofia Loukopoulou
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  4. Paraskevi Galina
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  5. Aimilia Mantzou
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  6. Tania Siahanidou
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Contributions

All the authors assisted with study design, acquisition, analysis and interpretation of the data; P.M. performed the clinical assessment; P.M. and E.P. were responsible for the flow cytometric analysis of circulating EPCs; P.G. was responsible for the ultrasound study of cIMT, aIMT, and FMD of the brachial artery and S.L. was responsible for cardiology data; A.M. was responsible for blood biochemistry. T.S. supervised the study. P.M. developed the first draft of the manuscript and T.S. critically reviewed it. All the authors edited the manuscript, revised it critically for important intellectual content, and approved the final version to be published.

Corresponding author

Correspondence to Tania Siahanidou.

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The authors declare no competing interests.

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Informed written consent was obtained from parents and children.

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Markopoulou, P., Papanikolaou, E., Loukopoulou, S. et al. Increased circulating endothelial progenitor cells (EPCs) in prepubertal children born prematurely: a possible link between prematurity and cardiovascular risk. Pediatr Res 90, 156–165 (2021). https://doi.org/10.1038/s41390-020-01190-y

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  • DOI: https://doi.org/10.1038/s41390-020-01190-y

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