The SK3 channel promotes placental vascularization by enhancing secretion of angiogenic factors

Rada, Cara C.; Murray, Grace; England, Sarah K.

doi:10.1152/ajpendo.00319.2014

Cited by 11 publications

(6 citation statements)

References 35 publications

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“…In the uteroplacental system, IKs and SKs participated in the regulation of contractility of uterine and placental vessels [90, 107, 109]. Moreover, SK3 was also involved in regulating uterine vascular remodeling and placental vascularization [110, 111]. Like BK Ca channels, E 2 β is required to maintain and to upregulate the expression and function of SKs in vasculature.…”

Section: E2β Signaling and Uteroplacental Circulation In Physiologmentioning

confidence: 99%

Effect of Oxidative Stress on the Estrogen-NOS-NO-K_Ca Channel Pathway in Uteroplacental Dysfunction: Its Implication in Pregnancy Complications

Song

Zhang

2019

Oxidative Medicine and Cellular Longevity

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During pregnancy, the adaptive changes in uterine circulation and the formation of the placenta are essential for the growth of the fetus and the well-being of the mother. The steroid hormone estrogen plays a pivotal role in this adaptive process. An insufficient blood supply to the placenta due to uteroplacental dysfunction has been associated with pregnancy complications including preeclampsia and intrauterine fetal growth restriction (IUGR). Oxidative stress is caused by an imbalance between free radical formation and antioxidant defense. Pregnancy itself presents a mild oxidative stress, which is exaggerated in pregnancy complications. Increasing evidence indicates that oxidative stress plays an important role in the maladaptation of uteroplacental circulation partly by impairing estrogen signaling pathways. This review is aimed at providing both an overview of our current understanding of regulation of the estrogen-NOS-NO-KCa pathway by reactive oxygen species (ROS) in uteroplacental tissues and a link between oxidative stress and uteroplacental dysfunction in pregnancy complications. A better understanding of the mechanisms will facilitate the development of novel and effective therapeutic interventions.

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Section: E2β Signaling and Uteroplacental Circulation In Physiologmentioning

confidence: 99%

Effect of Oxidative Stress on the Estrogen-NOS-NO-K_Ca Channel Pathway in Uteroplacental Dysfunction: Its Implication in Pregnancy Complications

Song

Zhang

2019

Oxidative Medicine and Cellular Longevity

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“…Нарушение механизмов вазоактивной регуляции процессов формирования ворсин и маточно-плацентарных кровеносных сосудов, наблюдаемое в условиях активной ЦМВ-инфекции у женщин, приводит к недостаточности снабжения кислородом, нарушению трофики и выведения через материнский кровоток продуктов фетоплацентарного метаболизма [13]. Возможно, хронический недостаток кислорода, высокий уровень прооксидантов и провоспалительных факторов, что было показано в более ранних наших работах [14,15] и в исследованиях других авторов [16], способствует изменению плацентарной перфузии, вызывающей инактивацию Ca2+-зависимого специфического ионотропного канала SK3 (регулятор тонуса сосудов) и отсоединению растворимой сплайс-формы от трансмембранного домена Flt-1 [17]. В результате поступающие и свободно циркулирующие в материнском кровотоке в условиях активной ЦМВ-инфекции высокие количества трофобластического sFlt-1 лимитируют экспрессию и биодоступность вазоактивных факторов PlGF и VEGF-A трофобластом и эндотелием сосудов [18], что приводит к задержке роста и дифференцировке ворсин, инвазии/миграции трофобласта и ограничению маточно-плацентарного ангиогенеза.…”

Section: Discussionunclassified

Features of vasoactive substance regulation in chorionic villi in women with spontaneous abortion and active cytomegalovirus infection

et al. 2022

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The aim of the study was to assess the levels of soluble fms-like tyrosine kinase 1 (sFlt1), placental growth factor (PlGF), and vascular endothelial growth factor A (VEGF-A) in tissue extracts in comparison with the histologic examination of the endometrium and chorionic villi in women with spontaneous abortion and active cytomegalovirus (CMV) infection.Materials and methods. 81 women at 7–9 weeks of pregnancy were examined: of them, 51 women were CMVseropositive with active infection and after spontaneous abortion, and 30 patients were CMV-seronegative, healthy women after therapeutic abortion. Immunoglobulins (Ig) M and G to CMV and CMV IgG avidity were measured in the blood plasma; sFlt1, PlGF, and VEGF-A were determined in extracts of chorionic villi by enzyme immunoassay. CMV DNA was detected in mononuclear cells of peripheral blood, urine, and chorionic villi by real-time polymerase chain reaction (PCR). A histologic examination of the endometrium and chorionic villi was carried out.Results. In chorionic villus extracts of women with spontaneous abortion and active CMV infection, the concentration of sFlt1 was 3.25 times higher (p < 0.001), and the levels of PlGF and VEGF-A were 1.31 (p < 0.001) and 2.16 times lower (p < 0.001) than in healthy women. A strong negative correlation was established between the levels of sFlt1 and PlGF (r = –0.702; p < 0.001) and VEGF-A (r = –0.858; p < 0.0005), and a positive correlation was revealed between PlGF and VEGF-A levels (r = 0.860; p < 0.001). According to the data of the histologic examination, a lag in decidual transformation of uterine vessels, trophoblast invasion, growth and differentiation of villi, and formation of fetal circulation was detected.Conclusion. The mechanisms of spontaneous abortion in women with active CMV infection include an imbalance of pro- and anti-angiogenic factors, which causes impaired placental development and uteroplacental circulation.

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“…Placenta formation and development are important processes for maintaining normal pregnancy, and normal placental blood vessel formation is a key link between them (32). Abnormal formation of placental blood vessels can lead to a variety of pregnancy complications, including PE (33). Blood vessel formation at the maternal-fetal interface is an important process in normal pregnancy (34).…”

Section: Discussionmentioning

confidence: 99%

Exosomal microRNA‑302a promotes trophoblast migration and proliferation, and represses angiogenesis by regulating the expression levels of VEGFA in preeclampsia

Zhao

et al. 2021

Mol Med Rep

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The global morbidity rate of preeclampsia (PE) is 3-7, and 10-20% of maternal deaths are associated with PE. However, the mechanism of its pathogenesis remains unknown. The aim of the present study was to examine the relationship between microRNA-302a (miR-302a) and PE. Firstly, the relative expression levels of miR-302a in placental tissues from patients with PE and normal controls were analyzed using reverse transcription-quantitative PCR. miR-302a expression was upregulated in PE tissues, particularly in severe PE. Subsequently, HTR-8/SVneo cells were transfected with miR-302a vectors to overexpress miR-302a. The overexpression of miR-302a markedly promoted cell proliferation, colony formation, migration and invasion in vitro. Subsequently, the present study examined the function of exosomes secreted by HTR-8/SVneo cells transfected with miR-302a vectors. Compared with the negative control vector group, miR-302a expression was markedly increased in exosomes in the miR-302a overexpression group. Additionally, exosomes with miR-302a overexpression had repressed HUVEC invasion and ring formation. The luciferase reporter assay indicated that VEGFA was a direct target of miR-302a, and miR-302a expression was negatively correlated with VEGFA expression. In conclusion, the present results demonstrated that upregulation of miR-302a may promote HTR-8/SVneo cell proliferation, migration and invasion, and repress angiogenesis by targeting VEGFA, indicating that miR-302a may be a potential target for the development of PE therapies.

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The SK3 channel promotes placental vascularization by enhancing secretion of angiogenic factors

Abstract: Rada CC, Murray G, England SK. The SK3 channel promotes placental vascularization by enhancing secretion of angiogenic factors.

Cited by 11 publications

References 35 publications

Effect of Oxidative Stress on the Estrogen-NOS-NO-K_Ca Channel Pathway in Uteroplacental Dysfunction: Its Implication in Pregnancy Complications

Effect of Oxidative Stress on the Estrogen-NOS-NO-K_Ca Channel Pathway in Uteroplacental Dysfunction: Its Implication in Pregnancy Complications

Features of vasoactive substance regulation in chorionic villi in women with spontaneous abortion and active cytomegalovirus infection

Exosomal microRNA‑302a promotes trophoblast migration and proliferation, and represses angiogenesis by regulating the expression levels of VEGFA in preeclampsia

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The SK3 channel promotes placental vascularization by enhancing secretion of angiogenic factors

Abstract: Rada CC, Murray G, England SK. The SK3 channel promotes placental vascularization by enhancing secretion of angiogenic factors.

Cited by 11 publications

References 35 publications

Effect of Oxidative Stress on the Estrogen-NOS-NO-KCa Channel Pathway in Uteroplacental Dysfunction: Its Implication in Pregnancy Complications

Effect of Oxidative Stress on the Estrogen-NOS-NO-KCa Channel Pathway in Uteroplacental Dysfunction: Its Implication in Pregnancy Complications

Features of vasoactive substance regulation in chorionic villi in women with spontaneous abortion and active cytomegalovirus infection

Exosomal microRNA‑302a promotes trophoblast migration and proliferation, and represses angiogenesis by regulating the expression levels of VEGFA in preeclampsia

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Effect of Oxidative Stress on the Estrogen-NOS-NO-K_Ca Channel Pathway in Uteroplacental Dysfunction: Its Implication in Pregnancy Complications

Effect of Oxidative Stress on the Estrogen-NOS-NO-K_Ca Channel Pathway in Uteroplacental Dysfunction: Its Implication in Pregnancy Complications