FKBPL and SIRT-1 Are Downregulated by Diabetes in Pregnancy Impacting on Angiogenesis and Endothelial Function
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 an...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2021.650328/full |
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| author | Abdelrahim Alqudah Abdelrahim Alqudah Kelly-Ann Eastwood Kelly-Ann Eastwood Djurdja Jerotic Naomi Todd Denise Hoch Ross McNally Danilo Obradovic Stefan Dugalic Alyson J. Hunter Valerie A. Holmes David R. McCance David R. McCance Ian S. Young Ian S. Young Chris J. Watson Tracy Robson Gernot Desoye David J. Grieve Lana McClements Lana McClements |
| author_facet | Abdelrahim Alqudah Abdelrahim Alqudah Kelly-Ann Eastwood Kelly-Ann Eastwood Djurdja Jerotic Naomi Todd Denise Hoch Ross McNally Danilo Obradovic Stefan Dugalic Alyson J. Hunter Valerie A. Holmes David R. McCance David R. McCance Ian S. Young Ian S. Young Chris J. Watson Tracy Robson Gernot Desoye David J. Grieve Lana McClements Lana McClements |
| author_sort | Abdelrahim Alqudah |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-19T00:44:11Z |
| format | Article |
| id | doaj.art-9da5fae60d9f4499b0224a5b05a2dc78 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-19T00:44:11Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-9da5fae60d9f4499b0224a5b05a2dc782022-12-21T20:44:20ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-06-011210.3389/fendo.2021.650328650328FKBPL and SIRT-1 Are Downregulated by Diabetes in Pregnancy Impacting on Angiogenesis and Endothelial FunctionAbdelrahim Alqudah0Abdelrahim Alqudah1Kelly-Ann Eastwood2Kelly-Ann Eastwood3Djurdja Jerotic4Naomi Todd5Denise Hoch6Ross McNally7Danilo Obradovic8Stefan Dugalic9Alyson J. Hunter10Valerie A. Holmes11David R. McCance12David R. McCance13Ian S. Young14Ian S. Young15Chris J. Watson16Tracy Robson17Gernot Desoye18David J. Grieve19Lana McClements20Lana McClements21The Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Northern Ireland, United KingdomDepartment of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmaceutical Sciences, The Hashemite University, Zarqa, JordanCentre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Northern Ireland, United KingdomRoyal Jubilee Maternity Hospital, Belfast Health and Social Care Trust, Northern Ireland, United KingdomMedical Faculty, University of Belgrade, Belgrade, SerbiaThe Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Northern Ireland, United KingdomDepartment of Gynaecology and Obstetrics, Medical University of Graz, Graz, AustriaThe Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Northern Ireland, United KingdomMedical Faculty, University of Belgrade, Belgrade, SerbiaClinic of Obstetrics and Gynecology, Clinical Centre of Serbia, Belgrade, SerbiaRoyal Jubilee Maternity Hospital, Belfast Health and Social Care Trust, Northern Ireland, United KingdomCentre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Northern Ireland, United KingdomCentre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Northern Ireland, United KingdomRoyal Victoria Hospital, Belfast Health and Social Care Trust, Northern Ireland, United KingdomCentre for Public Health, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Northern Ireland, United KingdomRoyal Victoria Hospital, Belfast Health and Social Care Trust, Northern Ireland, United KingdomThe Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Northern Ireland, United KingdomSchool of Pharmacy and Biomolecular Sciences, Irish Centre for Vascular Biology, RCSI University of Medicine and Health Sciences, Dublin, IrelandDepartment of Gynaecology and Obstetrics, Medical University of Graz, Graz, AustriaThe Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Northern Ireland, United KingdomThe Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Northern Ireland, United Kingdom0School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, NSW, AustraliaDiabetes 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.https://www.frontiersin.org/articles/10.3389/fendo.2021.650328/fullFKBPLSIRT-1GDMpregnancyangiogenesisDiabetes |
| spellingShingle | Abdelrahim Alqudah Abdelrahim Alqudah Kelly-Ann Eastwood Kelly-Ann Eastwood Djurdja Jerotic Naomi Todd Denise Hoch Ross McNally Danilo Obradovic Stefan Dugalic Alyson J. Hunter Valerie A. Holmes David R. McCance David R. McCance Ian S. Young Ian S. Young Chris J. Watson Tracy Robson Gernot Desoye David J. Grieve Lana McClements Lana McClements FKBPL and SIRT-1 Are Downregulated by Diabetes in Pregnancy Impacting on Angiogenesis and Endothelial Function Frontiers in Endocrinology FKBPL SIRT-1 GDM pregnancy angiogenesis Diabetes |
| title | FKBPL and SIRT-1 Are Downregulated by Diabetes in Pregnancy Impacting on Angiogenesis and Endothelial Function |
| title_full | FKBPL and SIRT-1 Are Downregulated by Diabetes in Pregnancy Impacting on Angiogenesis and Endothelial Function |
| title_fullStr | FKBPL and SIRT-1 Are Downregulated by Diabetes in Pregnancy Impacting on Angiogenesis and Endothelial Function |
| title_full_unstemmed | FKBPL and SIRT-1 Are Downregulated by Diabetes in Pregnancy Impacting on Angiogenesis and Endothelial Function |
| title_short | FKBPL and SIRT-1 Are Downregulated by Diabetes in Pregnancy Impacting on Angiogenesis and Endothelial Function |
| title_sort | fkbpl and sirt 1 are downregulated by diabetes in pregnancy impacting on angiogenesis and endothelial function |
| topic | FKBPL SIRT-1 GDM pregnancy angiogenesis Diabetes |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2021.650328/full |
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