FKBPL and SIRT-1 Are Downregulated by Diabetes in Pregnancy Impacting on Angiogenesis and Endothelial Function.

Autor:	Alqudah A; The Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Northern Ireland, United Kingdom.; Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmaceutical Sciences, The Hashemite University, Zarqa, Jordan., Eastwood KA; Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Northern Ireland, United Kingdom.; Royal Jubilee Maternity Hospital, Belfast Health and Social Care Trust, Northern Ireland, United Kingdom., Jerotic D; Medical Faculty, University of Belgrade, Belgrade, Serbia., Todd N; The Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Northern Ireland, United Kingdom., Hoch D; Department of Gynaecology and Obstetrics, Medical University of Graz, Graz, Austria., McNally R; The Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Northern Ireland, United Kingdom., Obradovic D; Medical Faculty, University of Belgrade, Belgrade, Serbia., Dugalic S; Clinic of Obstetrics and Gynecology, Clinical Centre of Serbia, Belgrade, Serbia., Hunter AJ; Royal Jubilee Maternity Hospital, Belfast Health and Social Care Trust, Northern Ireland, United Kingdom., Holmes VA; Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Northern Ireland, United Kingdom., McCance DR; Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Northern Ireland, United Kingdom.; Royal Victoria Hospital, Belfast Health and Social Care Trust, Northern Ireland, United Kingdom., Young IS; Centre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Northern Ireland, United Kingdom.; Royal Victoria Hospital, Belfast Health and Social Care Trust, Northern Ireland, United Kingdom., Watson CJ; The Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Northern Ireland, United Kingdom., Robson T; School of Pharmacy and Biomolecular Sciences, Irish Centre for Vascular Biology, RCSI University of Medicine and Health Sciences, Dublin, Ireland., Desoye G; Department of Gynaecology and Obstetrics, Medical University of Graz, Graz, Austria., Grieve DJ; The Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Northern Ireland, United Kingdom., McClements L; The Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Northern Ireland, United Kingdom.; School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW, Australia.
Jazyk:	angličtina
Zdroj:	Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2021 Jun 02; Vol. 12, pp. 650328. Date of Electronic Publication: 2021 Jun 02 (Print Publication: 2021).
DOI:	10.3389/fendo.2021.650328
Abstrakt:	Diabetes in pregnancy is associated with adverse pregnancy outcomes including preterm birth. Although the mechanisms leading to these pregnancy complications are still poorly understood, aberrant angiogenesis and endothelial dysfunction play a key role. FKBPL and SIRT-1 are critical regulators of angiogenesis, however, their roles in pregnancies affected by diabetes have not been examined before in detail. Hence, this study aimed to investigate the role of FKBPL and SIRT-1 in pre-gestational (type 1 diabetes mellitus, T1D) and gestational diabetes mellitus (GDM). Placental protein expression of important angiogenesis proteins, FKBPL, SIRT-1, PlGF and VEGF-R1, was determined from pregnant women with GDM or T1D, and in the first trimester trophoblast cells exposed to high glucose (25 mM) and varying oxygen concentrations [21%, 6.5%, 2.5% (ACH-3Ps)]. Endothelial cell function was assessed in high glucose conditions (30 mM) and following FKBPL overexpression. Placental FKBPL protein expression was downregulated in T1D (FKBPL; p<0.05) whereas PlGF/VEGF-R1 were upregulated (p<0.05); correlations adjusted for gestational age were also significant. In the presence of GDM, only SIRT-1 was significantly downregulated (p<0.05) even when adjusted for gestational age (r=-0.92, p=0.001). Both FKBPL and SIRT-1 protein expression was reduced in ACH-3P cells in high glucose conditions associated with 6.5%/2.5% oxygen concentrations compared to experimental normoxia (21%; p<0.05). FKBPL overexpression in endothelial cells (HUVECs) exacerbated reduction in tubule formation compared to empty vector control, in high glucose conditions (junctions; p<0.01, branches; p<0.05). In conclusion, FKBPL and/or SIRT-1 downregulation in response to diabetic pregnancies may have a key role in the development of vascular dysfunction and associated complications affected by impaired placental angiogenesis. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2021 Alqudah, Eastwood, Jerotic, Todd, Hoch, McNally, Obradovic, Dugalic, Hunter, Holmes, McCance, Young, Watson, Robson, Desoye, Grieve and McClements.)
Databáze:	MEDLINE
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