Angiogenic Properties of Placenta-Derived Extracellular Vesicles in Normal Pregnancy and in Preeclampsia

Gebara, Natalia; Correia, Yolanda; Wang, Keqing; Bussolati, Benedetta

doi:10.3390/ijms22105402

Cited by 24 publications

(16 citation statements)

References 103 publications

(130 reference statements)

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“…PE has a great impact on growth and development of the fetus, impairs the structure and function of fetal cardiovascular system or kidney, and causes hypertension. 15 Current studies suggest that the pathogenesis of PE may be related to decidual macrophage dysfunction, 16 placental angiogenesis disorder, 17 placental aging, 18 , 19 protein aggregation, and defective placental aggregation phagocytosis. 20 At the molecular level, the microRNA spectrum of blood exosomes has been used to evaluate the pathophysiology of preeclampsia and predict the disease, 21 and there are more and more studies at gene level.…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Network Analysis Identifies Potential Targets for Prevention of Preeclampsia

Yu¹,

Zhao²,

Sun³

et al. 2022

IJGM

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Objective Preeclampsia (PE) is a pregnancy-specific multisystem disease as well as an important cause of maternal and perinatal death. This study aimed to analyze the placental transcriptional data and clinical information of PE patients available in the published database and predict the target genes for prevention of PE. Methods The clinical information and corresponding RNA data of PE patients were downloaded from the GEO database. Cluster analysis was performed to examine the correlation between different genotyping genes and clinical manifestations. Then, bioinformatic approaches including GO, KEGG, WGCNA, and GSEA were employed to functionally characterize candidate target genes involved in pathogenesis of PE. Results Two PE datasets GSE60438 and GSE75010 were obtained and combined, thereby providing the data of 205 samples in total (100 non-PE and 105 PE samples). After eliminating the batch effect, we grouped and analyzed the integrated data, and further performed GSEA analysis. It was found that the genes in group 1 and group 2 were different from those in normal samples. Moreover, WGCNA analysis revealed that genes in group 1 were up-regulated in turquoise module, including SASH1 , PIK3CB and FLT-1 , while genes in group 2 were up-regulated in the blue and brown modules. We further conducted GO and KEGG pathway enrichment analyses and found that the differential genes in turquoise module were mainly involved in biological processes such as small molecular catabolic process, while being highly enriched in pathways, including MAPK signaling pathway and Rap1 signaling pathway. Conclusion FLT-1 was conventionally used to predict PE risk, and sFLT-1 could also be used as an indicator to evaluate PE treatment effect. As a candidate biomarker for predicting PE, SASH1 may participate in proliferation, migration, invasion and epithelial mesenchymal transformation of human trophoblast cells by regulating MAPK pathway and Rap1 signaling pathway, thus affecting the progression of PE. The mechanism allowing PIK3CB to regulate PE development was not clear, while the gene could be another candidate biomarker for PE risk prediction. This is an exploratory study and our findings were still required verification in further studies.

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Section: Discussionmentioning

confidence: 99%

Gene Expression Network Analysis Identifies Potential Targets for Prevention of Preeclampsia

Yu¹,

Zhao²,

Sun³

et al. 2022

IJGM

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“…In pregnancy, EVs can stimulate or impede angiogenesis based on their content and molecular expression, dependent on the cell of origin and its pathophysiological state [ 77 ]. Hypoxic conditions modulate the release of EVs from cytotrophoblast and placental cells in the first trimester of the pregnancy [ 78 ].…”

Section: The Importance Of Exosomes In Pregnancy: Focus On Angiogenesismentioning

confidence: 99%

The implications of exosomes in pregnancy: emerging as new diagnostic markers and therapeutics targets

et al. 2022

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Extracellular vehicles (EVs) are a heterogeneous group of cell and membranous particles originating from different cell compartments. EVs participate in many essential physiological functions and mediate fetal-maternal communications. Exosomes are the smallest unit of EVs, which are delivered to the extracellular space. Exosomes can be released by the umbilical cord, placenta, amniotic fluid, and amniotic membranes and are involved in angiogenesis, endothelial cell migration, and embryo implantation. Also, various diseases such as gestational hypertension, gestational diabetes mellitus (GDM), preterm birth, and fetal growth restriction can be related to the content of placental exosomes during pregnancy. Due to exosomes' ability to transport signaling molecules and their effect on sperm function, they can also play a role in male and female infertility. In the new insight, exosomal miRNA can diagnose and treat infertilities disorders. In this review, we focused on the functions of exosomes during pregnancy.

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“…A functional and adequately vascularized placenta is crucial for a healthy pregnancy and birth outcome (Wu et al, 2004). Placental dysfunction results in a decrease in the angiogenic vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) and the release of deleterious placental factors including sFIt1 into the maternal circulation causing generalized endothelial dysfunction (Gebara et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

“…Placental dysfunction results in a decrease in the angiogenic vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) and the release of deleterious placental factors including sFIt1 into the maternal circulation causing generalized endothelial dysfunction (Gebara et al, 2021). Nitric oxide (NO) donors have potent vasodilator effects and have been shown to improve blood flow in the feto‐placental circulation of pregnancies affected by mild preeclampsia (Luzi et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

l‐Citrulline ameliorates pathophysiology in a rat model of superimposed preeclampsia

Man

Zhou

Lam

et al. 2022

British J Pharmacology

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Background and Purpose Preeclampsia, characterized by hypertension, proteinuria and restriction of fetal growth, is one of the leading causes of maternal and perinatal mortality. So far, there is no effective pharmacological therapy for preeclampsia. The present study was conducted to investigate the effects of supplementation with l‐citrulline in Dahl salt‐sensitive rats, a model of superimposed preeclampsia. Experimental Approach Parental Dahl salt‐sensitive rats were treated with l‐citrulline (2.5 g·L−1 in drinking water) from the day of mating to the end of lactation period. Blood pressure was monitored throughout pregnancy and markers of preeclampsia were assessed. Endothelial function of the pregnant Dahl salt‐sensitive rats was assessed by wire myograph. Key Results In Dahl salt‐sensitive rats, l‐citrulline supplementation significantly reduced maternal blood pressure, proteinuria and levels of circulating soluble fms‐like tyrosine kinase 1. l‐Citrulline improved maternal endothelial function by augmenting the production of nitric oxide in the aorta and improving endothelium‐derived hyperpolarizing factor‐mediated vasorelaxation in resistance arteries. l‐Citrulline supplementation improved placental insufficiency and fetal growth, which were associated with an enhancement of angiogenesis and reduction of fibrosis and senescence in the placentas. In addition, l‐citrulline down‐regulated genes involved in the TLR4 and NF‐κB signalling pathways. Conclusion and Implications This study shows that l‐citrulline supplementation reduced gestational hypertension and improved placentation and fetal growth in a rat model of superimposed preeclampsia. l‐Citrulline supplementation may provide an effective and safe therapeutic strategy for preeclampsia that benefits both the mother and the fetus.

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Angiogenic Properties of Placenta-Derived Extracellular Vesicles in Normal Pregnancy and in Preeclampsia

Cited by 24 publications

References 103 publications

Gene Expression Network Analysis Identifies Potential Targets for Prevention of Preeclampsia

Gene Expression Network Analysis Identifies Potential Targets for Prevention of Preeclampsia

The implications of exosomes in pregnancy: emerging as new diagnostic markers and therapeutics targets

l‐Citrulline ameliorates pathophysiology in a rat model of superimposed preeclampsia

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