ArticleFrontiers in endocrinology2021
FKBPL and SIRT-1 Are Downregulated by Diabetes in Pregnancy Impacting on Angiogenesis and Endothelial Function.
Article in Frontiers in endocrinology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 44 citations in OpenAlex.
- Gestational diabetes mellitus and vascular malperfusion lesions in the placenta: A systematic review and meta-analysis.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2025Pooled it
- Placenta-derived small extracellular vesicles transfer miR-520d-5p to mediate pancreatic β-cell injury in gestational diabetes mellitus by targeting SIRT1.BMC pregnancy and childbirth · 2026Article
- Article
- Sirtuins in Women's Health.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Maternal Immune Activation: Implications for Congenital Heart Defects.Clinical reviews in allergy & immunology · 2025Review
- Increased Preeclampsia Risk in GDM Pregnancies: The Role of SIRT1 rs12778366 Polymorphism and Telomere Length.International journal of molecular sciences · 2025Article
- Sirtuins and Their Implications in the Physiopathology of Gestational Diabetes Mellitus.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Influence of gestational diabetes mellitus on the cardiovascular system and its underlying mechanisms.Frontiers in endocrinology · 2025Review
- First Trimester Placental Biomarkers for Pregnancy Outcomes.International journal of molecular sciences · 2024Review
- Effect of SIRT1 gene single-nucleotide polymorphisms on susceptibility to type 1 diabetes in a Han Chinese population.Journal of endocrinological investigation · 2024Article
- Endothelial progenitor cells in pregnancy-related diseases.Clinical science (London, England : 1979) · 2023Review
- The emerging importance of immunophilins in fibrosis development.Molecular and cellular biochemistry · 2023Review
- E-Cigarette Aerosol Condensate Leads to Impaired Coronary Endothelial Cell Health and Restricted Angiogenesis.International journal of molecular sciences · 2023Article
- FK506-Binding Protein like (FKBPL) Has an Important Role in Heart Failure with Preserved Ejection Fraction Pathogenesis with Potential Diagnostic Utility.Biomolecules · 2023Article
- A placenta-on-a-chip model to determine the regulation of FKBPL and galectin-3 in preeclampsia.Cellular and molecular life sciences : CMLS · 2023Article
- Pathophysiological impact of CXC and CX3CL1 chemokines in preeclampsia and gestational diabetes mellitus.Frontiers in cell and developmental biology · 2023Review
- Recent progress in metabolic reprogramming in gestational diabetes mellitus: a review.Frontiers in endocrinology · 2023Review
- Hyperglycemia disturbs trophoblast functions and subsequently leads to failure of uterine spiral artery remodeling.Frontiers in endocrinology · 2023Review
- Decreased Cardiac NOX4 and SIRT-1 Protein Levels Contribute to Decreased Angiogenesis in the Heart of Diabetic Rats: Rescue Effects of IGF-1 and Exercise.Advanced pharmaceutical bulletin · 2023Article
- Vascular endothelial growth factor and its receptors regulation in gestational diabetes mellitus and eclampsia.Journal of translational medicine · 2022Review
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 5 countries.
Funding
Abstract
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.
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