scholarly journals SUCNR1 is Expressed in Human Placenta and Mediates Angiogenesis: Significance in Gestational Diabetes

2021 ◽  
Author(s):  
Reham Atallah ◽  
Jürgen Gindlhuber ◽  
Wolfgang Platzer ◽  
Thomas Bärnthaler ◽  
Eva Tatzl ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Gestational Diabetes ◽  
Human Placenta ◽  
Umbilical Vein ◽  
Placental Tissue ◽  
Vegf Gene ◽  
Placental Angiogenesis ◽  
Arterial Endothelial Cells

Placental hypervascularization has been reported in pregnancy-related pathologies such as gestational diabetes mellitus (GDM). Nevertheless, the underlying causes behind this abnormality are not well understood. In this study, we addressed the expression of SUCNR1 (cognate succinate receptor) in human placental endothelial cells and hypothesized that succinate-SUCNR1 axis might play a role in the placental hypervascularization reported in GDM. We measured significantly higher succinate levels in placental tissue lysates from women with GDM relative to matched controls. In parallel, SUCNR1 protein expression was upregulated in GDM tissue lysates as well as in isolated diabetic fetoplacental arterial endothelial cells (FpECAds). A positive correlation of SUCNR1 and vascular endothelial growth factor (VEGF) protein levels in tissue lysates indicated a potential link between succinate-SUCNR1 axis and placental angiogenesis. In our in-vitro experiments, succinate prompted hallmarks of angiogenesis in human umbilical vein endothelial cells (HUVECs) such as proliferation, migration and spheroid sprouting. These results were further validated in fetoplacental arterial endothelial cells (FpECAs), where succinate induced endothelial tube formation. VEGF gene expression was increased in response to succinate in both HUVECs and FpECAs. Yet, knockdown of SUCNR1 in HUVECs led to suppression of VEGF gene expression and abrogated the migratory ability and wound healing in response to succinate. In conclusion, our data underline SUCNR1 as a promising metabolic target in human placenta and as a potential driver of enhanced placental angiogenesis in GDM.

scholarly journals SUCNR1 Is Expressed in Human Placenta and Mediates Angiogenesis: Significance in Gestational Diabetes

2021 ◽  
Vol 22 (21) ◽  
pp. 12048
Author(s):  
Reham Atallah ◽  
Juergen Gindlhuber ◽  
Wolfgang Platzer ◽  
Thomas Bärnthaler ◽  
Eva Tatzl ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Gestational Diabetes ◽  
Human Placenta ◽  
Umbilical Vein ◽  
Placental Tissue ◽  
Vegf Gene ◽  
Placental Angiogenesis ◽  
Arterial Endothelial Cells

Placental hypervascularization has been reported in pregnancy-related pathologies such as gestational diabetes mellitus (GDM). Nevertheless, the underlying causes behind this abnormality are not well understood. In this study, we addressed the expression of SUCNR1 (cognate succinate receptor) in human placental endothelial cells and hypothesized that the succinate–SUCNR1 axis might play a role in the placental hypervascularization reported in GDM. We measured significantly higher succinate levels in placental tissue lysates from women with GDM relative to matched controls. In parallel, SUCNR1 protein expression was upregulated in GDM tissue lysates as well as in isolated diabetic fetoplacental arterial endothelial cells (FpECAds). A positive correlation of SUCNR1 and vascular endothelial growth factor (VEGF) protein levels in tissue lysates indicated a potential link between the succinate–SUCNR1 axis and placental angiogenesis. In our in vitro experiments, succinate prompted hallmarks of angiogenesis in human umbilical vein endothelial cells (HUVECs) such as proliferation, migration and spheroid sprouting. These results were further validated in fetoplacental arterial endothelial cells (FpECAs), where succinate induced endothelial tube formation. VEGF gene expression was increased in response to succinate in both HUVECs and FpECAs. Yet, knockdown of SUCNR1 in HUVECs led to suppression of VEGF gene expression and abrogated the migratory ability and wound healing in response to succinate. In conclusion, our data underline SUCNR1 as a promising metabolic target in human placenta and as a potential driver of enhanced placental angiogenesis in GDM.

scholarly journals In vitro effects of low-level aldehyde exposures on human umbilical vein endothelial cells

2015 ◽  
Vol 4 (5) ◽  
pp. 1250-1259 ◽  
Author(s):  
Nuan P. Cheah ◽  
Jeroen L.A. Pennings ◽  
Jolanda P. Vermeulen ◽  
Roger W.L. Godschalk ◽  
Frederik J. van Schooten ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cardiovascular Disease ◽  
Endothelial Cells ◽  
Tobacco Smoke ◽  
Umbilical Vein ◽  
Human Umbilical Vein ◽  
In Vitro Effects ◽  
Umbilical Vein Endothelial Cells ◽  
Disease Exposure

Aldehydes cause gene expression changes for genes associated with cardiovascular disease. Exposure to aldehydes from tobacco smoke needs to be controlled.

scholarly journals A Randomised, Controlled Study of Different Glycaemic Targets during Gestational Diabetes Treatment: Effect on the Level of Adipokines in Cord Blood and ANGPTL4 Expression in Human Umbilical Vein Endothelial Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
P. Popova ◽  
L. Vasilyeva ◽  
A. Tkachuck ◽  
M. Puzanov ◽  
A. Golovkin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Gestational Diabetes ◽  
Cord Blood ◽  
Umbilical Vein ◽  
Fasting Blood Glucose ◽  
Controlled Study ◽  
Control Group ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

Our aim was to study the expression of adipokine-encoding genes (leptin, adiponectin, and angiopoietin-like protein 4 (ANGPTL4)) in human umbilical vein endothelial cells (HUVECs) and adipokine concentration in cord blood from women with gestational diabetes mellitus (GDM) depending on glycaemic targets. GDM patients were randomised to 2 groups per target glycaemic levels: GDM1 (tight glycaemic targets, fasting blood glucose < 5.1 mmol/L and <7.0 mmol/L postprandial, N=20) and GDM2 (less tight glycaemic targets, <5.3 mmol/L and < 7.8 mmol/L, respectively, N=21). The control group included 25 women with normal glucose tolerance. ANGPTL4 expression was decreased in the HUVECs from GDM patients versus the control group (23.11 ± 5.71, 21.47 ± 5.64, and 98.33 ± 20.92, for GDM1, GDM2, and controls; p<0.001) with no difference between GDM1 and GDM2. The level of adiponectin gene expression was low and did not differ among the groups. Leptin gene expression was undetectable in HUVECs. In cord blood, leptin/adiponectin ratio (LAR) was increased in GDM2 compared to controls and GDM1 (p=0.038) and did not differ between GDM1 and controls. Tight glycaemic targets were associated with normalisation of increased LAR in the cord blood. ANGPTL4 expression was downregulated in HUVECs of newborns from GDM mothers and was not affected by the intensity of glycaemic control.

scholarly journals Conditioned medium from primary cytotrophoblasts, primary placenta-derived mesenchymal stem cells, or sub-cultured placental tissue promoted HUVECs angiogenesis in vitro

2021 ◽  
Author(s):  
haiying ma ◽  
Shenglu Jiang ◽  
Lili Du ◽  
Jinfang Liu ◽  
Xiaoyan Xu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Early Pregnancy ◽  
Human Placenta ◽  
Placental Tissue ◽  
Antibody Array ◽  
Placental Angiogenesis ◽  
Placental Cells

Abstract Background As a large capillary network, the human placenta plays an important role throughout pregnancy. Placental vascular development is complex and delicate and involves many types of placental cells, such as trophoblasts, and mesenchymal stem cells. There has been no systematic, comparative study on the roles of these two groups of placental cells and the whole placental tissue in the placental angiogenesis. In this study, primary cytotrophoblasts (CTBs) from early-pregnancy and primary human placenta-derived mesenchymal stem cells (hPDMSCs) from different stages of pregnancy were selected as the cell research objects, and full-term placental tissue was selected as the tissue research object to detect the effects of their conditioned medium (CM) on HUVECs angiogenesis. Methods We successfully isolated primary hPDMSCs and CTBs, collected CM from these placental cells and sub-cultured placental tissue, and then evaluated the effects of the CM on a series of angiogenic processes in HUVECs in vitro. Furthermore, we measured the levels of angiogenic factors in the CM of placental cells or tissue by an angiogenesis antibody array. Results The results showed that not only placental cells but also sub-cultured placental tissue, to some extent, promoted HUVECs angiogenesis in vitro by promoting proliferation, adhesion, migration, invasion, and tube formation. We also found that primary placental cells in early pregnancy, whether CTBs or hPDMSCs, played more significant roles than those in full-term pregnancy. Placental cells-derived CM collected at 24 hours or 48 hours had the best effect and sub-cultured placental tissue-derived CM collected at 7 days had the best effect among all the different time points. The semiquantitative angiogenesis antibody array showed that 18 of the 43 angiogenic factors had obvious spots in placental cells-derived CM or sub-cultured placental tissue-derived CM, and the levels of 5 factors (including CXCL-5, GRO, IL-6, IL-8, and MCP-1) were the highest in sub-cultured placental tissue-derived CM. Conclusions CM obtained from placental cells (primary CTBs or hPDMSCs) or sub-cultured placental tissue contained proangiogenic factors and promoted HUVECs angiogenesis in vitro. Therefore, our research is helpful to better understand placental angiogenesis regulation and provides theoretical support for the clinical application of placental components, especially sub-cultured placental tissue-derived CM, in vascular tissue engineering and clinical treatments.

scholarly journals C-Type Natriuretic Peptide (CNP) Inhibition of Interferon-γ-Mediated Gene Expression in Human Endothelial Cells In Vitro

Biosensors ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 86
Author(s):  
Amy Day ◽  
Zoe Jameson ◽  
Carolyn Hyde ◽  
Bigboy Simbi ◽  
Robert Fowkes ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Inflammatory Responses ◽  
Umbilical Vein ◽  
Vascular Inflammation ◽  
Western World ◽  
Human Endothelial Cells ◽  
Ifn Γ

Cardiovascular diseases, including atherosclerosis, now account for more deaths in the Western world than from any other cause. Atherosclerosis has a chronic inflammatory component involving Th1 pro-inflammatory cytokines such as IFN-γ, which is known to induce endothelial cell inflammatory responses. On the other hand CNP, which acts via its receptors to elevate intracellular cGMP, is produced by endothelium and endocardium and is upregulated in atherosclerosis. It is believed to be protective, however its role in vascular inflammation is not well understood. The aim of this study was to investigate the effects of CNP on human endothelial cell inflammatory responses following IFN-γ stimulation. Human umbilical vein endothelial cells were treated with either IFN-γ (10 ng/mL) or CNP (100 nm), or both in combination, followed by analysis by flow cytometry for expression of MHC class I and ICAM-1. IFN-γ significantly increased expression of both molecules, which was significantly inhibited by CNP or the cGMP donor 8-Bromoguanosine 3’,5’-cyclic monophosphate (1 µm). CNP also reduced IFN-γ mediated kynurenine generation by the IFN-γ regulated enzyme indoleamine-2,3-deoxygenase (IDO). We conclude that CNP downmodulates IFN-γ induced pro-inflammatory gene expression in human endothelial cells via a cGMP-mediated pathway. Thus, CNP may have a protective role in vascular inflammation and novel therapeutic strategies for CVD based on upregulation of endothelial CNP expression could reduce chronic EC inflammation.

Effect of ambient oxygen on cultured endothelial cells from different vascular beds

1987 ◽  
Vol 253 (4) ◽  
pp. H878-H883 ◽  
Author(s):  
H. W. Farber ◽  
D. M. Center ◽  
S. Rounds
Keyword(s):  
Endothelial Cells ◽  
Tissue Injury ◽  
Umbilical Vein ◽  
Human Umbilical Vein ◽  
Ambient Oxygen ◽  
Pulmonary Arterial ◽  
Vascular Beds ◽  
Umbilical Vein Endothelial Cells ◽  
Arterial Endothelial Cells

By the use of production of neutrophil chemoattractant activity as a marker, we investigated the responsiveness of endothelial cells of four different anatomic origins to altered ambient oxygen tension to determine whether genetic or conditioned variation existed. The ability of bovine aortic, bovine pulmonary arterial, bovine coronary arterial, and human umbilical vein endothelial cells incubated in decreased oxygen concentrations to release neutrophil chemoattractant activity was assessed. Bovine aortic, human umbilical vein, and bovine coronary arterial endothelial cells produce neutrophil chemoattractant activity in response to 10 or 3% ambient oxygen in vitro. In contrast, 0% ambient oxygen is required for appearance of neutrophil chemoattractant activity from pulmonary artery endothelial cells. These studies suggest that there may be genetic or conditioned variations in the response of endothelium from different vascular beds to decreased oxygen tensions. Furthermore, endothelial cells may play a role in neutrophil-mediated tissue injury during ischemia.

scholarly journals Gestational Diabetes Type 2: Variation in High-Density Lipoproteins Composition and Function

2020 ◽  
Vol 21 (17) ◽  
pp. 6281
Author(s):  
Yael Pasternak ◽  
Tal Biron-Shental ◽  
Meital Ohana ◽  
Yael Einbinder ◽  
Nissim Arbib ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Gestational Diabetes ◽  
Placental Tissue ◽  
Diabetes Type 2 ◽  
High Density ◽  
Apolipoprotein A1 ◽  
High Density Lipoproteins ◽  
Long Term Effects ◽  
And Function

Aims: Class A2 gestational diabetes mellitus (GDMA2) has short- and long-term effects on the mother and child. These may include abnormalities of placentation, damage to endothelial cells and cardiovascular disease. This research investigated the function and composition of high-density lipoproteins (HDL) among women with GDMA2 and their fetuses. Methods: Thirty pregnant women were recruited during admission for delivery. The function and expression of HDL, paraoxonase1 (PON1) and apolipoprotein A1 (APOA1) in the blood samples and the placental tissue were evaluated. The effect of HDL on migration of endothelial cells was measured in vitro. Results: Compared to normal pregnancy (NP), APOA1 in the maternal plasma of women with GDMA2 was decreased. More APOA1 and PON1 were released from HDL of women with GDMA2, compared to NP. Placental APOA1 and PON1 were decreased in GDMA2. For endothelial cells stimulated with TNFα, HDL cell migration was decreased when cells were evaluated with NP-HDL, as compared to GDMA2-HDL. Conclusions: GDMA2 affects the composition and function of HDL in plasma. Changes in HDL commonly seen in GDMA2 were observed in maternal and placental samples, but not in cord samples. These results might indicate a placental role in protecting the fetus by preserving the components and functions of HDL and require further investigation.

scholarly journals Efficient Lytic Infection of Human Arterial Endothelial Cells by Human Cytomegalovirus Strains

2000 ◽  
Vol 74 (16) ◽  
pp. 7628-7635 ◽  
Author(s):  
M. Kahl ◽  
D. Siegel-Axel ◽  
S. Stenglein ◽  
G. ◽  
Jahn ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Human Cytomegalovirus ◽  
Umbilical Vein ◽  
Lytic Infection ◽  
Vascular Bed ◽  
Complete Lysis ◽  
Infected Cells ◽  
Arterial Endothelial Cells

ABSTRACT Endothelial cells (EC) are common targets of permissive infection by human cytomegalovirus (HCMV) in vivo during acute disease. However, studies of HCMV-EC interactions in vitro have generated discordant results. While lytic infection of cultured venous EC has been well established, Fish et al. (K. N. Fish, C. Soderberg Naucler, L. K. Mills, S. Stenglein, and J. A. Nelson, J. Virol. 72:5661–5668) have reported noncytopathic persistence of the virus in cultured aortic EC. We propose that interstrain differences in viral host cell tropism rather than the vascular bed of origin of infected EC might account for these discrepancies. In the present investigation we compared the responses of EC derived from human adult iliac artery, placental microvasculature, and umbilical vein to infection with various HCMV strains. Regardless of the vascular bed of origin, infection with EC-propagated HCMV strains induced 100% efficient cytopathic change progressing to complete lysis of inoculated monolayers. While fibroblast-propagated strains persisted at low titer in infected arterial EC cultures, they were also cytolytic for individual infected cells. The finding of cytopathic lytic infection of arterial EC by HCMV implicates a mechanism of vascular injury in the pathogenesis of HCMV infection.

scholarly journals Conditioned medium from primary cytotrophoblasts, primary placenta-derived mesenchymal stem cells, or sub-cultured placental tissue promoted HUVEC angiogenesis in vitro

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Haiying Ma ◽  
Shenglu Jiang ◽  
Lili Du ◽  
Jinfang Liu ◽  
Xiaoyan Xu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Early Pregnancy ◽  
Human Placenta ◽  
Placental Tissue ◽  
Antibody Array ◽  
Placental Angiogenesis ◽  
Placental Cells

Abstract Background As a large capillary network, the human placenta plays an important role throughout pregnancy. Placental vascular development is complex and delicate and involves many types of placental cells, such as trophoblasts, and mesenchymal stem cells. There has been no systematic, comparative study on the roles of these two groups of placental cells and the whole placental tissue in the placental angiogenesis. In this study, primary cytotrophoblasts (CTBs) from early pregnancy and primary human placenta-derived mesenchymal stem cells (hPDMSCs) from different stages of pregnancy were selected as the cell research objects, and full-term placental tissue was selected as the tissue research object to detect the effects of their conditioned medium (CM) on human umbilical vein endothelial cell (HUVEC) angiogenesis. Methods We successfully isolated primary hPDMSCs and CTBs, collected CM from these placental cells and sub-cultured placental tissue, and then evaluated the effects of the CM on a series of angiogenic processes in HUVECs in vitro. Furthermore, we measured the levels of angiogenic factors in the CM of placental cells or tissue by an angiogenesis antibody array. Results The results showed that not only placental cells but also sub-cultured placental tissue, to some extent, promoted HUVEC angiogenesis in vitro by promoting proliferation, adhesion, migration, invasion, and tube formation. We also found that primary placental cells in early pregnancy, whether CTBs or hPDMSCs, played more significant roles than those in full-term pregnancy. Placental cell-derived CM collected at 24 h or 48 h had the best effect, and sub-cultured placental tissue-derived CM collected at 7 days had the best effect among all the different time points. The semiquantitative angiogenesis antibody array showed that 18 of the 43 angiogenic factors had obvious spots in placental cell-derived CM or sub-cultured placental tissue-derived CM, and the levels of 5 factors (including CXCL-5, GRO, IL-6, IL-8, and MCP-1) were the highest in sub-cultured placental tissue-derived CM. Conclusions CM obtained from placental cells (primary CTBs or hPDMSCs) or sub-cultured placental tissue contained proangiogenic factors and promoted HUVEC angiogenesis in vitro. Therefore, our research is helpful to better understand placental angiogenesis regulation and provides theoretical support for the clinical application of placental components, especially sub-cultured placental tissue-derived CM, in vascular tissue engineering and clinical treatments.

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