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dc.contributor.authorSultan, S.A.*
dc.contributor.authorLiu, Wanting*
dc.contributor.authorPeng, Yonghong*
dc.contributor.authorRoberts, Wayne*
dc.contributor.authorWhitelaw, D.C.*
dc.contributor.authorGraham, Anne M.*
dc.date.accessioned2016-09-21T15:45:55Z
dc.date.available2016-09-21T15:45:55Z
dc.date.issued2015
dc.identifier.citationSultan SA, Liu W, Peng Y et al (2015) The Role of Maternal Gestational Diabetes in Inducing Fetal Endothelial Dysfunction. Journal of Cellular Physiology. 230(11): 2695-2705.
dc.identifier.urihttp://hdl.handle.net/10454/9230
dc.descriptionNo
dc.description.abstractGestational diabetes mellitus (GDM) is known to be associated with fetal endothelial dysfunction, however, the mechanisms are not fully understood. This study examines the effect of maternal diabetes on fetal endothelial function and gene expression under physiological glucose conditions (5 mM). Human umbilical vein endothelial cell (HUVEC) isolated from diabetic mothers (d.HUVEC) grew more slowly than HUVEC isolated from healthy mothers (c.HUVEC) and had delayed doubling time despite increased levels of total vascular endothelial growth factor (VEGF) expression and protein production as determined by real-time PCR and ELISA respectively. Using western blot, the levels of antiproliferative VEGF165b isoform were increased in d.HUVEC relative to c.HUVEC. Successful VEGF165b knockdown by small interfering RNA (siRNA) resulted in increased proliferation of d.HUVEC measured by MTT, compared with negative siRNA control, to similar levels measured in c.HUVEC. In addition, d.HUVEC generated excess levels of ROS as revealed by 2',7' Dichlorodihydrofluorescein Diacetate (DCFH-DA) and Nitrotetrazolium blue (NBT). Using microarray, 102 genes were differentially overexpressed between d.HUVEC versus c.HUVEC (>1.5-fold change; P < 0.05). Functional clustering analysis of these differentially expressed genes revealed participation in inflammatory responses (including adhesion) which may be related to pathological outcomes. Of these genes, ICAM-1 was validated as upregulated, confirming microarray results. Additional confirmatory immunofluorescence staining revealed increased protein expression of ICAM-1 compared with c.HUVEC which was reduced by vitamin C treatment (100 muM). Thus, maternal diabetes induces persistent alterations in fetal endothelial function and gene expression following glucose normalization and antioxidant treatment could help reverse endothelium dysfunction.
dc.relation.isreferencedbyhttp://dx.doi.org/10.1002/jcp.24993
dc.subjectCell proliferation
dc.subject; Diabetes
dc.subject; Endothelial cells
dc.subject; Female
dc.subject; Gene expression regulation
dc.subject; Gene knockout techniques
dc.subject; Glucose
dc.subject; Human umbilical vein endothelial cells
dc.subject; Humans
dc.subject; Intercellular adhesion molecule-1
dc.subject; Pregnancy
dc.subject; Protein isoforms
dc.subject; Umbilical veins
dc.subject; Vascular endothelial growth factor A
dc.titleThe Role of Maternal Gestational Diabetes in Inducing Fetal Endothelial Dysfunction
dc.status.refereedYes
dc.typeArticle
dc.type.versionNo full-text available in the repository


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