scholarly journals FKBPL and SIRT-1, key angiogenesis proteins, are downregulated by diabetes in pregnancy

2020 ◽  
Author(s):  
Abdelrahim Alqudah ◽  
Kelly-Ann Eastwood ◽  
Djurdja Jerotic ◽  
Naomi Todd ◽  
Denise Hoch ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Protein Expression ◽  
Gestational Age ◽  
High Glucose ◽  
Cell Function ◽  
First Trimester ◽  
Diabetes In Pregnancy ◽  
Endothelial Cell Function ◽  
In Pregnancy

AbstractContextDiabetes in pregnancy is associated with numerous complications, however the mechanisms are still poorly understood.ObjectiveTo investigate the role of new angiogenesis markers, FKBPL and SIRT-1, in pre-gestational (type 1 diabetes, T1D) and gestational diabetes (GDM).Design and interventionPlacental FKBPL, SIRT-1, PlGF and VEGF-R1 protein expression was determined from pregnant women with GDM or T1D, and in first trimester trophoblast cells exposed to high glucose and varying oxygen concentrations. Endothelial cell function was assessed in high glucose conditions and FKBPL overexpression.Settings and ParticipantsHuman placental samples from pregnant women with GDM (n=6) or T1D (n=8) were collected to assess FKBPL and SIRT-1 protein expression compared to non-diabetic controls.Main outcome measuresTo determine the role of placental FKBPL and/or SIRT-1 in diabetic pregnancies, in first trimester trophoblasts and endothelial cell function in high-glucose environment.ResultsPlacental 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 (p<0.001) was significantly downregulated even when adjusted for gestational age (r=-0.92, p=0.001). FKBPL and SIRT-1 were also downregulated in ACH-3P cells in high glucose conditions and 6.5%/2.5% oxygen concentrations (p<0.05). FKBPL overexpression in HUVECs reduced tubule formation compared to empty vector control, in high glucose conditions (junctions; p<0.01, branches; p<0.05).ConclusionsFKBPL and/or SIRT-1 downregulation in response to diabetes may have a role in the development of vascular dysfunction in pregnancy, and associated complications such as preeclampsia.

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

2021 ◽  
Vol 12 ◽  
Author(s):  
Abdelrahim Alqudah ◽  
Kelly-Ann Eastwood ◽  
Djurdja Jerotic ◽  
Naomi Todd ◽  
Denise Hoch ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Protein Expression ◽  
Gestational Age ◽  
High Glucose ◽  
Cell Function ◽  
Diabetes In Pregnancy ◽  
Tubule Formation ◽  
Endothelial Cell Function ◽  
In Pregnancy ◽  
Oxygen Concentrations

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&lt;0.05) whereas PlGF/VEGF-R1 were upregulated (p&lt;0.05); correlations adjusted for gestational age were also significant. In the presence of GDM, only SIRT-1 was significantly downregulated (p&lt;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&lt;0.05). FKBPL overexpression in endothelial cells (HUVECs) exacerbated reduction in tubule formation compared to empty vector control, in high glucose conditions (junctions; p&lt;0.01, branches; p&lt;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.

Enhanced Vascular Endothelial Cell Function on Nanostructured Titanium Surface Features: The Role of Nano to Submicron Roughness

2008 ◽  
Vol 1136 ◽  
Author(s):  
Jing Lu ◽  
Dongwoo Khang ◽  
Thomas J. Webster
Keyword(s):  
Cell Adhesion ◽  
Endothelial Cell ◽  
Cell Function ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Endothelial Cell Function ◽  
Titanium Surfaces ◽  
Endothelial Cell Adhesion

ABSTRACTTo study the contribution of different surface feature properties in improving vascular endothelial cell adhesion, rationally designed nano/sub-micron patterns with various dimensions were created on titanium surfaces in this study. In vitro results indicated that endothelial cell adhesion was improved when the titanium pattern dimensions decreased into the nano-scale. Specifically, endothelial cells preferred to adhere on sub-micron and nano rough titanium substrates compared to flat titanium. Moreover, titanium with nano and sub-micron roughness and with the same chemistry as compared to flat titanium, had significantly greater surface energy. Thus, the present study indicated the strong potential of surface nanotopography and nano/sub-micron roughness for improving current vascular stent design.

High Glucose Alters Endothelial Cell Response to Shear Stress

2009 ◽  
Author(s):  
Steven F. Kemeny ◽  
Alisa Morss Clyne
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Endothelial Cell ◽  
Blood Vessels ◽  
Cell Mechanics ◽  
High Glucose ◽  
Fluid Shear Stress ◽  
Cell Function ◽  
Focal Adhesions ◽  
Endothelial Cell Function

Endothelial cells line the walls of all blood vessels, where they maintain homeostasis through control of vascular tone, permeability, inflammation, and the growth and regression of blood vessels. Endothelial cells are mechanosensitive to fluid shear stress, elongating and aligning in the flow direction [1–2]. This shape change is driven by rearrangement of the actin cytoskeleton and focal adhesions [2]. Hyperglycemia, a hallmark of diabetes, affects endothelial cell function. High glucose has been shown to increase protein kinase C, formation of glucose-derived advanced glycation end-products, and glucose flux through the aldose reductase pathway within endothelial cells [3]. These changes are thought to be related to increased reactive oxygen species production [4]. While endothelial cell mechanics have been widely studied in healthy conditions, many disease states have yet to be explored. Biochemical alterations related to high glucose may alter endothelial cell mechanics.

scholarly journals The role of BMPs in endothelial cell function and dysfunction

2014 ◽  
Vol 25 (9) ◽  
pp. 472-480 ◽  
Author(s):  
Laura A. Dyer ◽  
Xinchun Pi ◽  
Cam Patterson
Keyword(s):  
Endothelial Cell ◽  
Cell Function ◽  
Endothelial Cell Function

The Evolving Role of MicroRNAs in Endothelial Cell Dysfunction in Response to Infection

2018 ◽  
Vol 44 (03) ◽  
pp. 216-223 ◽  
Author(s):  
Rebecca Watkin ◽  
Glenn Fitzpatrick ◽  
Steve Kerrigan
Keyword(s):  
Endothelial Cell ◽  
Cardiovascular System ◽  
Noncoding Rna ◽  
Target Genes ◽  
Cell Function ◽  
Critical Role ◽  
Microbial Infection ◽  
Endothelial Cell Function ◽  
Rna Molecules

AbstractThe microRNAs are short noncoding RNA molecules responsible for translational repression and silencing of target genes via binding to the mRNA. They are found in all eukaryotic cells and play a critical role in virtually all physiological processes, including within the cardiovascular system where they influence cellular development, differentiation, cardiovascular function, hemostasis, and programmed cell death. Dysregulated microRNA expression is associated with several conditions ranging from cancer and autoimmune disease to infection. Progressively, it has become increasingly clear that microRNAs are important components of the host response to microbes. The cardiovascular system, coupled with cells of the innate immune system, provide the initial interaction and first response to microbial infection, respectively. This review presents the current state of knowledge regarding the role of microRNAs with emphasis on their role in controlling endothelial cell function.

Glucose and Insulin Modulate the Capacity of Endothelial Cells (HUVEC) to Express P-selectin and Bind a Monocytic Cell Line (U937)

2001 ◽  
Vol 86 (08) ◽  
pp. 680-685 ◽  
Author(s):  
Kamal Chettab ◽  
Jacques Duhault ◽  
Elisabeth Koenig-Berard ◽  
John McGregor ◽  
Marta Puente Navazo
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Line ◽  
High Glucose ◽  
Cell Function ◽  
Leukocyte Adhesion ◽  
Human Umbilical Cord ◽  
Monocytic Cell ◽  
Monocytic Cell Line ◽  
Endothelial Cell Function

SummaryDiabetes mellitus is associated with increased prevalence of endothelial cell dysfunction and vascular diseases. Mechanisms leading to alterations in endothelial cell function are poorly understood. We report here that hyperglycaemia results in the expression of endothelial adhesion molecules involved in leukocyte adhesion and extravasation. Incubation of human umbilical cord endothelial cells (HUVEC) with 25 mM glucose induced the expression of P-selectin. This effect was reversed by the addition of 1 nM insulin. Moreover, increased ICAM-1 expression was observed upon HUVEC incubation with 25 mM glucose. Increased adhesion of U937 cells (a monocytic cell line) to endothelial cells cultured with 25 mM glucose was observed. High glucose-induced monocytes cell adhesion was inhibited by an anti-P-selectin monoclonal antibody (LYP20). These results show that high glucose concentration activates endothelial cells leading to monocytes adhesion providing further evidence that hyperglycaemia might be implicated in vessel wall lesions contributing to diabetic vascular disease.Present address: Dr. M. D. Puente Navazo, Centre Pluridisciplinaire d’Oncologie, ISREC, Epalinges, Switzerland

scholarly journals Effect of the Anti-retroviral Drugs Efavirenz, Tenofovir and Emtricitabine on Endothelial Cell Function: Role of PARP

2017 ◽  
Vol 17 (4) ◽  
pp. 393-404 ◽  
Author(s):  
Mary Faltz ◽  
Hild Bergin ◽  
Elly Pilavachi ◽  
Guy Grimwade ◽  
Jon G. Mabley
Keyword(s):  
Endothelial Cell ◽  
Cell Function ◽  
Endothelial Cell Function

scholarly journals Up-regulation of Delta-like 4 Ligand in Human Tumor Vasculature and the Role of Basal Expression in Endothelial Cell Function

2005 ◽  
Vol 65 (19) ◽  
pp. 8690-8697 ◽  
Author(s):  
Nilay S. Patel ◽  
Ji-Liang Li ◽  
Daniele Generali ◽  
Richard Poulsom ◽  
David W. Cranston ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Function ◽  
Human Tumor ◽  
Tumor Vasculature ◽  
Endothelial Cell Function ◽  
Basal Expression
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