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Acta Diabetologica

, Volume 56, Issue 1, pp 73–85 | Cite as

The effect of maternal type 2 diabetes on fetal endothelial gene expression and function

  • Samar SultanEmail author
Original Article
  • 110 Downloads

Abstract

Aims

Maternal type 2 diabetes (T2D) can result in adverse pathological outcomes to both the mother and fetus. The present study aimed to investigate the pathological effects of maternal T2D on the gene expression patterns and functions of fetal human umbilical vein endothelial cells (HUVECs), a representative of fetal vascular cells.

Methods

Cell proliferation, apoptosis, mitochondrial ROS production and cell cycle were measured using flowcytometry. Genome-wide expression was measured using Affymetrix microarray. Gene expression of CCND2, STAT1, ITGB8, ALDH2, and ADAMTS5 was measured using real-time PCR.

Results

HUVECs derived from T2D mothers (T2D-HUVECs) showed elevated levels of mitochondrial superoxide anions, reduced cell proliferation, and increased apoptosis rates relative to HUVECs derived from healthy control mothers (C.HUVECs). In addition , T2D-HUVECs showed a decreased proportion of cells in G0/G1 and cell cycle arrest at the S phases relative to controls. Interestingly, microarray experiments revealed significant differences in genome-wide expression profiles between T2D-HUVECs and C.HUVECs. In particular, the analysis identified 90 upregulated genes and 42 downregulated genes. The upregulated genes CCND2, STAT1, ITGB8, ALDH2, and ADAMTS5 were validated as potential biomarkers for fetal endothelial dysfunction. Functional network analysis revealed that these genes are the important players that participate in the pathogenesis of endothelial dysfunction, which in turn influences the inflammatory response, cellular movement, and cardiovascular system development and function.

Conclusion

Sustained alterations in the overall function of T2D-HUVEC and gene expression profiles provided insights into the role of maternal T2D on the pathophysiology of the fetal endothelial dysfunction.

Keywords

Type 2 diabetes Endothelial cells Oxidative stress Genome-wide gene expression Dysfunction 

Abbreviations

MMPs

ADAMTS are zinc metalloproteases

AGE

Advanced glycation end products

ECs

Endothelial cells

ET-1

Endothelin 1

ECM

Extracellular matrix

GDM

Gestational diabetes mellitus

C.HUVEC

Healthy control cells

T2D-HUVECs

HUVECs derived from T2D mothers

T2D

Type 2 diabetes

NO

Nitric oxide

PKC

Protein kinase C

PI

Propidium iodide

ROS

Reactive oxygen species

Notes

Acknowledgements

The author is grateful for mothers who donated cords and nurses who helped with sample collection in Gynecology and Obstetrics department at King Abdulaziz University Hospital. This work was supported by a grant from King Abdulaziz City for Science and Technology (KACST) Grant no 35-180. The author is also grateful to Dr. H. Schulten, Dr. S. Karim, Dr. F, Ahmed and staff from microarray and Bioinformatics unit at the Center of Excellence in Genomic Medicine Research (CEGMR) for their help and technical assistance.

Compliance with ethical standards

Conflict of interest

Author declared that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Approval of the study was given by the Ethics Committee of the King Abdulaziz University Hospital, Jeddah, Saudi Arabia.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

592_2018_1207_MOESM1_ESM.docx (57 kb)
Supplementary material 1 (DOCX 57 KB)

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Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Medical Technology Department, Faculty of Applied Medical SciencesKing Abdulaziz UniversityJeddahSaudi Arabia

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