Gestational diabetes mellitus is associated with increased pro-migratory activation of vascular endothelial growth factor receptor 2 and reduced expression of vascular endothelial growth factor receptor 1

Troncoso, Felipe; Acurio, Jesenia; Herlitz, Kurt; Aguayo, Claudio; Bertoglia, Patricio; Guzmán-Gutiérrez, Enrique; Loyola, Marco; González, Marcelo; Rezgaoui, Meriem; Desoyé, Gernot; Escudero, Carlos

doi:10.1371/journal.pone.0182509

Cited by 46 publications

(41 citation statements)

References 51 publications

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“…вероятно, при нарушении углеводного обмена на начальных стадиях запускаются резервные возможности защиты эндотелия и стимулируется ангиогенез. в пользу данной гипотезы свидетельствует более высокий уровень PigF во всех группах с гсд по сравнению с группами без гсд, как с ПЭ, так и без ПЭ, а также известный по данным литературы высокий уровень VegF при гсд, большая масса и разветвленность сосудистой сети плацент при гсд по сравнению с таковой у пациенток без нарушений углеводного обмена [11,13,23,24]. Полученные данные дополняют существующие единичные исследования относительно ценности маркеров ангиогенеза в прогнозировании ПЭ у пациенток с гсд [10,25].…”

Section: Discussionunclassified

“…среди прочих патогенетических моментов заслуживают внимания вклад антиангиогенных факторов в развитие ПЭ при гсд и их предиктивная ценность в развитии ПЭ у пациенток с гсд. исследования, посвященные данной проблеме, крайне немногочисленны и противоречивы [10][11][12][13][14].…”

Section: обоснованиеunclassified

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Preeclampsia features in pregnancy with gestational diabetes mellitus

Bettikher¹,

Dedov²,

Popova³

et al. 2019

Z.akus.zen.bolezn

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Hypothesis/aims of study. The high prevalence of gestational diabetes mellitus (GDM) and the social importance of preeclampsia (PE) due to massive perinatal morbidity and mortality, as well as the high rate of PE in GDM pregnancy define the need to study the characteristics of pregnancy course in these women to develop the prevention and management of pregnancy complication. This study aimed at evaluating clinical and laboratory features of PE in GDM pregnancy. Study design, materials and methods. According to the inclusion criteria, 112 pregnant women were enrolled in this prospective cohort study after 24 weeks of gestation: with GDM and PE (n = 24), with PE (n = 22); with GDM (n = 37), without studied pregnancy complications (n = 37). We assessed serum levels of placental growth factor (PIGF) and soluble FMS-like tyrosine kinase-1 (sFlt-1). Pregnancy course and labour were evaluated using medical history. Results. Severe PE developed more often (p = 0.0014, Chi-square test) in the PE group (59%, n = 13) compared to the GDM + PE group (13%, n = 3). Elective preterm labour occurred more often in the PE group compared to other study groups (PE: 23%, n = 5; GDM + PE: 9%, n = 2; p 0.0001, Chi-square test with Yates correction), which is in line with the severity of PE in this group. The rate of preterm labour did not differ between the GDM + PE group and the group without studied pregnancy complications. Moreover, the mean fasting glucose level was higher in the GDM group compared to the GDM + PE group (p = 0.01, MannWhitney test). The GDM + PE group was characterized by fasting hyperglycemia episodes and a basal insulin regimen, while the GDM group by postprandial glucose peaks, and a bolus insulin regimen. Women with GDM + PE were notable for the high pre-pregnancy body mass index (29.0 6.58 kg/m2), and a family history of DM was more typical for women with GDM without PE (59%, n = 19). The sFlt-1/PIGF ratio did not differ between the GDM + PE, GDM and control groups and was lower compared to the PE group (p 0.0001, Fishers LSD test). PIGF level was not different in the GDM + PE and GDM groups, but was lower compared to the control group. Conclusion. Our study showed that PE in women with GDM is more benign than in patients without GDM, taking into account both clinical and laboratory signs. At the same time, obesity appears to be one of the most important risk factors for the both pregnancy complications. The data of this study, in addition to those described in the literature, suggest that initial carbohydrate disorders play a disease-limiting, protective role in a vicious cycle of PE due to angiogenesis stimulation. The use of angiogenesis factors as markers of PE in GDM patients is limited, which requires further research.

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Section: Discussionunclassified

Section: обоснованиеunclassified

Preeclampsia features in pregnancy with gestational diabetes mellitus

Bettikher¹,

Dedov²,

Popova³

et al. 2019

Z.akus.zen.bolezn

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“…Cell migration was analyzed in vitro as described [ 37 , 38 ]. Briefly, cells were allowed to reach confluence in growth medium, and switched to serum-free medium.…”

Section: Methodsmentioning

confidence: 99%

“…Tubes were photographed using inverted phase contrast microscope under 10× magnification (Olympus, Tokyo, Japan). Formation of networks (branches) was quantified using the “Angiogenesis Analyzer” plugin from ImageJ 1.48 software as previously reported [ 37 , 38 ].…”

Section: Methodsmentioning

confidence: 99%

Advantages in Wound Healing Process in Female Mice Require Upregulation A2A-Mediated Angiogenesis under the Stimulation of 17β-Estradiol

Troncoso

Herlitz

Acurio

et al. 2020

IJMS

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Estrogenic steroids and adenosine A2A receptors promote the wound healing and angiogenesis processes. However, so far, it is unclear whether estrogen may regulate the expression and pro-angiogenic activity of A2A receptors. Using in vivo analyses, we showed that female wild type (WT) mice have a more rapid wound healing process than female or male A2A-deficient mice (A2AKO) mice. We also found that pulmonary endothelial cells (mPEC) isolated from female WT mice showed higher expression of A2A receptor than mPEC from male WT mice. mPEC from female WT mice were more sensitive to A2A-mediated pro-angiogenic response, suggesting an ER and A2A crosstalk, which was confirmed using cells isolated from A2AKO. In those female cells, 17β-estradiol potentiated A2A-mediated cell proliferation, an effect that was inhibited by selective antagonists of estrogen receptors (ER), ERα, and ERβ. Therefore, estrogen regulates the expression and/or pro-angiogenic activity of A2A adenosine receptors, likely involving activation of ERα and ERβ receptors. Sexual dimorphism in wound healing observed in the A2AKO mice process reinforces the functional crosstalk between ER and A2A receptors.

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“…[45]. В противовес этим результатам в исследовании Troncoso et al (2017) установлены более низкие уровни экспрессии flt-1 в плаценте при ГСД по сравнению с группой контроля [46] (см. табл.…”

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Possibilities for prediction and prevention of preeclampsia in women with diabetes mellitus

Kapustin

Викторович

2018

Z.akus.zen.bolezn

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Based on the analysis of literature data, the role and serum levels of the main angiogenic (placental growth factor (PlGF)) and antiangiogenic vascular factors (endoglin (sENG), soluble fms-like type 1 tyrosine kinase (sFlt-1)) have been assessed in pregnant women with different types of diabetes mellitus (DM) in both the plasma and placenta. We evaluated the effectiveness of administration of low doses of acetylsalicylic acid for preventing preeclampsia in diabetic pregnancy. In addition, the effectiveness of using the sFlt-1/PlGF and PlGF/sENG ratios as possible test systems for prediction of the complication in this patient population was evaluated. It has been found that the synthesis of the studied biomarkers fails in the diabetic pregnancy, with the expression levels of sENG and sFlt-1 increased and PlGF reduced. However, the insufficient research does not allow us to make unambiguous conclusions about the practical validity of the evaluation of the plasma content of these vascular factors and their ratios for the preeclampsia prediction in pregnant women with DM. The presented data on acetylsalicylic acid administration to these women are also controversial. Given the high incidence of adverse perinatal outcomes associated with DM during pregnancy, an additional assessment of the prognostic risk model for the development of preeclampsia and the appropriateness of aspirin administration is needed. Therefore, further randomized studies are required to address this issue.

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Gestational diabetes mellitus is associated with increased pro-migratory activation of vascular endothelial growth factor receptor 2 and reduced expression of vascular endothelial growth factor receptor 1

Cited by 46 publications

References 51 publications

Preeclampsia features in pregnancy with gestational diabetes mellitus

Preeclampsia features in pregnancy with gestational diabetes mellitus

Advantages in Wound Healing Process in Female Mice Require Upregulation A2A-Mediated Angiogenesis under the Stimulation of 17β-Estradiol

Possibilities for prediction and prevention of preeclampsia in women with diabetes mellitus

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