Vitamin D restores angiogenic balance and decreases tumor necrosis factor‐α in a rat model of pre‐eclampsia

Jing, Song; Li, Yue; An, Ruifang

doi:10.1111/jog.13186

Cited by 31 publications

(19 citation statements)

References 47 publications

(83 reference statements)

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“…Although sFlt‐1 is commonly increased in preeclampsia and experimental hypertension‐in‐pregnancy, no differences were observed in sFlt‐1 plasmatic levels in HTN‐Preg animals, as previously reported in different animal models of hypertension‐in‐pregnancy . Also, glucocorticoids, such as desoxycorticosterone acetate may present anti‐inflammatory effects and since reductions in inflammation have been related to decreases in sFlt‐1, such effect of desoxycorticosterone acetate may have blunted increases in sFlt‐1 in our hypertensive pregnant animals. Moreover, PlGF plasmatic levels were diminished in Preg+NaHS, HTN‐Preg and HTN‐Preg+NaHS groups.…”

Section: Discussionsupporting

confidence: 73%

Increases in placental nitric oxide, but not nitric oxide‐mediated relaxation, underlie the improvement in placental efficiency and antihypertensive effects of hydrogen sulphide donor in hypertensive pregnancy

Possomato-Vieira

Chimini

Silva

et al. 2018

Clin Exp Pharma Physio

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Dysregulation of hydrogen sulphide (H S) producing enzymes has been related to hypertensive pregnancy, and H S donor, sodium hydrosulphide (NaHS) exerts antihypertensive effects, modulates angiogenic factors production and acts as an antioxidant. Moreover, reduction in nitric oxide (NO) bioavailability is related to hypertensive pregnancy and H S may interact with NO, modulating its production. We aimed to investigate the NaHS effects in hypertension-in-pregnancy and also in feto-placental parameters. Female Wistar rats (200-250 g) were mated and desoxycorticosterone acetate injections followed by replacement of water by 0.9% saline solution were used to induce hypertensive pregnancy. Rats were divided into four groups: normal pregnant (Norm-Preg), pregnant + NaHS (Preg+NaHS), hypertensive pregnant (HTN-Preg) and HTN-Preg+NaHS. Systolic blood pressure was increased in HTN-Preg and this increase was blunted in HTN-Preg+NaHS. Fetal and placental weights were decreased in HTN-Preg animals, while fetal growth restriction was improved in HTN-Preg+NaHS. Placental weight was lower in HTN-Preg+NaHS than in HTN-Preg; however, placental efficiency was re-established in HTN-Preg+NaHS rats. We observed that a partial contribution of placental NO, but not changes in anti-angiogenic factors may mediate the increases in placental efficiency in HTN-Preg+NaHS. HTN-Preg presented thoracic aorta hyperreactivity to phenylephrine while NaHS treatment blunted this hyperreactivity, which seems not to be related to NO-mediated relaxation induced by acetylcholine. Therefore, changes in vascular responsiveness promoted by NaHS treatment may underlie the beneficial effects in systolic blood pressure and feto-placental parameters in our study.

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Section: Discussionsupporting

confidence: 73%

Increases in placental nitric oxide, but not nitric oxide‐mediated relaxation, underlie the improvement in placental efficiency and antihypertensive effects of hydrogen sulphide donor in hypertensive pregnancy

Possomato-Vieira

Chimini

Silva

et al. 2018

Clin Exp Pharma Physio

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“…38 Similarly, the role of vitamin D in restoring angiogenic balance by increasing VEGF levels has also been demonstrated in a pregnancy-induced hypertension rat model. 39 In our study, the size of the official cavities and the number of official cavity-like structures formed by MSCs treated with 1,25(OH) 2 D 3 were significantly increased. After blocking the VDR channel with pyridoxal-5-phosphate, the cell-to-tube capacity of MSCs was significantly weakened, demonstrating that 1,25(OH) 2 D 3 promotes vasculogenesis of MSCs, which is mediated by the VDR.…”

Section: Discussionsupporting

confidence: 50%

1,25(OH)2D3 Strengthens the Vasculogenesis of Multipotent Mesenchymal Stromal Cells from Rat Bone Marrow by Regulating the PI3K/AKT Pathway

Weng

Lin

et al. 2020

DDDT

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Background: Multipotent mesenchymal stromal cells (MSCs) have recently been reported to promote vasculogenesis by differentiating into endothelial cells and releasing numerous cytokines and paracrine factors. However, due to low cell activity, their potential for clinical application is not very satisfactory. This study aimed to explore the effects and mechanisms of 1,25-dihydroxyvitamin D (1,25(OH) 2 D 3) on the vasculogenesis of MSCs. Methods: MSCs were isolated from the femurs and tibias of rats and characterized by flow cytometry. After treatment with different concentrations of 1,25(OH) 2 D 3 (0 µM, 0.1 µM and 1 µM), the proliferation of MSCs was analyzed by Cell Counting Kit-8 (CCK-8), and the migratory capability was measured by Transwell assays and cell scratch tests. Capillary-like structure formation was observed by using Matrigel. Western blotting was used to detect the expression of FLK-1 and vWF to investigate the differentiation of MSCs into endothelial cells. Western blotting and gelatin zymography were used to detect the expression and activities of VEGF, MMP-2 and MMP-9 secreted by MSCs under the influence of 1,25(OH) 2 D 3. Finally, the VDR antagonist pyridoxal-5-phosphate (P5P) and the PI3K/AKT pathway inhibitor LY294002 were utilized to test the phosphorylation levels of key kinases in the PI3K/AKT pathway by Western blotting and the formation of capillary-like structures in Matrigel. Results: The proliferation and migratory capability of MSCs and the ability of MSCs to form a tube-like structure in Matrigel were enhanced after treatment with 1,25(OH) 2 D 3. Moreover, MSCs treated with 1,25(OH) 2 D 3 showed high expression of vWF and Flk-1. There was a significant increase in the expression of VEGF, MMP-2 and MMP-9 secreted by MSCs treated with 1,25(OH) 2 D 3, as well as in the activity of MMP-2 and MMP-9. The phosphorylation level of AKT increased with time after 1,25(OH) 2 D 3 treatment, while LY294002 weakened AKT phosphorylation. In addition, the ability to form capillary-like structures was reduced when the VDR and PI3K/AKT pathways were blocked. Conclusion: This study confirmed that 1,25(OH) 2 D 3 treatment can strengthen the ability of MSCs to promote vasculogenesis in vitro, and the mechanism may be related to the activation of the PI3K/AKT pathway.

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“…In their post-hoc analysis derived from the VDAART RCT, Mirzakhani et al ( 17 ) reported that a key factor in preventing preeclampsia was vitamin D status early in pregnancy: first trimester circulating 25(OH)D concentration of a least 100 nmol/L (40 ng/mL) was associated with a reduction in the risk of developing preeclampsia. Predicted by both observational studies as well as experimental animal models, the association of vitamin D deficiency and its ability to alter placental development and embryo implantation is further supported by the findings of Mirzakhani et al ( 15 , 17 , 103 , 104 ). As mentioned earlier, this effect is likely vitamin D-mediated during a very early point in pregnancy.…”

Section: Vitamin D-induced Genomic Alterations During Pregnancymentioning

confidence: 72%

The Implications of Vitamin D Status During Pregnancy on Mother and her Developing Child

2018

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Pregnancy is a time of tremendous growth and physiological changes for mother and her developing fetus with lifelong implications for the child. The concert of actions that must occur so mother does not reject the foreign tissue of the fetus is substantial. There must be exquisite balance between maternal tolerance to these foreign proteins of paternal origin but also immune surveillance and function such that the mother is not immunocompromised. When this process goes awry, the mother may experience such pregnancy complications as preeclampsia and infections. Vitamin D deficiency affects these processes. Controversy continues with regard to the optimal daily intake of vitamin D, when sunlight exposure should be taken into account, and how to define sufficiency during such vulnerable and critical periods of development. The importance of vitamin D supplementation during pregnancy in preventing some of the health risks to the mother and fetus appears linked to achieving 25(OH)D concentrations >40 ng/mL, the beginning point of the plateau where conversion of the vitamin D metabolite 25(OH)D, the pre-hormone, to 1,25(OH)2D, the active hormone, is optimized. Throughout pregnancy, the delivery of adequate vitamin D substrate—through sunlight or supplement—is required to protect both mother and fetus, and when in sufficient supply, favorably impacts the epigenome of the fetus, and in turn, long term health. There is a growing need for future research endeavors to focus not only on critical period(s) from pre-conception through pregnancy, but throughout life to prevent certain epigenetic changes that adversely affect health. There is urgency based on emerging research to correct deficiency and maintain optimal vitamin D status. The impact of vitamin D and its metabolites on genetic signaling during pregnancy in both mother and fetus is an area of great activity and still in its early stages. While vitamin D repletion during pregnancy minimizes the risk of certain adverse outcomes (e.g., preterm birth, asthma, preeclampsia, and gestational diabetes), the mechanisms of how these processes occur are not fully understood. As we intensify our research efforts in these areas. it is only a matter of time that such mechanisms will be defined.

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Vitamin D restores angiogenic balance and decreases tumor necrosis factor‐α in a rat model of pre‐eclampsia

Abstract: Vitamin D supplementation plays an important role in restoring angiogenic balance and reducing inflammation in pregnancy-induced hypertension.

Cited by 31 publications

References 47 publications

Increases in placental nitric oxide, but not nitric oxide‐mediated relaxation, underlie the improvement in placental efficiency and antihypertensive effects of hydrogen sulphide donor in hypertensive pregnancy

Increases in placental nitric oxide, but not nitric oxide‐mediated relaxation, underlie the improvement in placental efficiency and antihypertensive effects of hydrogen sulphide donor in hypertensive pregnancy

<p>1,25(OH)<sub>2</sub>D<sub>3</sub> Strengthens the Vasculogenesis of Multipotent Mesenchymal Stromal Cells from Rat Bone Marrow by Regulating the PI3K/AKT Pathway</p>

The Implications of Vitamin D Status During Pregnancy on Mother and her Developing Child

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