The defect of both angiogenesis and lymphangiogenesis is involved in preeclampsia

Liu, H.; Li, Y.; Zhang, J.; Rao, Meghan; Liang, Haiying; Liu, G.

doi:10.1016/j.placenta.2014.12.013

Cited by 32 publications

(22 citation statements)

References 34 publications

(34 reference statements)

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“…The more frequent occurrence of PE in women with hypertension prior to pregnancy could be indicative of such a relationship 49 . In this regard, a recent study found evidence of impaired decidual angiogenesis (and lymphangiogenesis) in these patients 50 . With regard to specific cell types, molecular defects in the decidua have been described early in pregnancy before for the signs of PE appear 51 .…”

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confidence: 93%

Why is placentation abnormal in preeclampsia?

Fisher

2015

American Journal of Obstetrics and Gynecology

510

316

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The causes of preeclampsia remain one of the great medical mysteries of our time. This syndrome is thought to occur in two stages with abnormal placentation leading to a maternal inflammatory response. Specific regions of the placenta have distinct pathological features. During normal pregnancy, cytotrophoblasts emigrate from the chorionic villi and invade the uterus, reaching the inner third of the myometrium. This unusual process is made even more exceptional by the fact that the placental cells are hemi-allogeneic, co-expressing maternal and paternal genomes. Within the uterine wall, cytotrophoblasts deeply invade the spiral arteries. Cytotrophoblasts migrate up these vessels and replace, in a retrograde fashion, the maternal endothelial lining. They also insert themselves amongst the smooth muscle cells that form the tunica media. As a result, the spiral arteries attain the physiological properties that are required to adequately perfuse the placenta. In comparison, invasion of the venous side of the uterine circulation is minimal, sufficient to enable venous return. In preeclampsia, cytotrophoblast invasion of the interstitial uterine compartment is frequently shallow, although not consistently so. In many locations, spiral artery invasion is incomplete. There are many fewer endovascular cytotrophoblasts and some vessels retain portions of their endothelial lining with relatively intact muscular coats while others are not modified. Work from our group showed that these defects mirror deficits in the differentiation program that enables cytotrophoblast invasion of the uterine wall. During normal pregnancy, invasion is accompanied by downregulation of epithelial-like molecules that are indicative of their ectodermal origin and upregulation of numerous receptors and ligands that are typically expressed by endothelial or vascular smooth muscle cells. For example, the expression of epithelial-cadherin, the cell-cell adhesion molecule that many ectodermal derivatives use to adhere to one another, becomes nearly undetectable, replaced by vascular-endothelial cadherin, which serves the same purpose in blood vessels. Invading cytotrophoblasts also modulate vascular endothelial growth factor ligands and receptors, at some point in the differentiation process expressing every (mammalian) family member. Molecules in this family play crucial roles in vascular and trophoblast biology, including prevention of apoptosis. In preeclampsia, this process of vascular mimicry is incomplete, which we theorize hinders the cells interactions with spiral arterioles. What causes these aberrations? Given what is known from animal models and human risk factors, reduced placental perfusion and/or certain disease states (metabolic, immune and cardiovascular) lie upstream. Recent evidence suggests the surprising conclusion that isolation and culture of cytotrophoblasts from the placentas of pregnancies complicated by preeclampsia enables normalization of their gene expression. The affected molecules include SEMA3B, which downregulates vas...

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confidence: 93%

Why is placentation abnormal in preeclampsia?

Fisher

2015

American Journal of Obstetrics and Gynecology

510

316

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“…27,28 In fact, lymphatics are present in immunologically privileged organs including T-cell tolerance. [9][10][11][12] To overcome this limitation, we evaluated the lymphatic system using immunostaining to assess both lymphaticspecific markers and the vascular morphology. 28,34 Additionally, antigen-presenting cells that migrate through lymphatic vessels interact with naive T cells in the draining lymph that lymphatics are present in the maternal decidua but not in the placenta itself and that lymphatic growth is induced by cytotrophoblasts.…”

Section: Discussionmentioning

confidence: 99%

“…25 Nonetheless, the presence of lymphatic systems at the maternal-fetal interface remains inconclusive as many studies failed to perform phenotypical and morphological evaluations using lymphatic-specific markers or the unique structure of lymphatic vessels, respectively. [9][10][11][12] To overcome this limitation, we evaluated the lymphatic system using immunostaining to assess both lymphaticspecific markers and the vascular morphology. Using this approach, multilayered LYVE1-positive lymphatic vessels were identified in the uterine wall of a pregnant mouse and confirmed in human decidua.…”

Section: Discussionmentioning

confidence: 99%

“…8 To date, studies of placental lymphatic development have been limited and have provided different or opposing conclusions. [9][10][11][12] Various immune cells including macrophages, natural killer cells, dendritic cells, T cells, and regulatory T cells (Treg) are present in the decidua and are required for the proper invasion of trophoblasts during placentation. [13][14][15] Tregs are an endogenous T-cell population that normally functions to suppress adaptive and innate immune responses and prevent autoimmune disease.…”

Section: Introductionmentioning

confidence: 99%

“…6,7 Changes in the lymphatic vascular network can lead to various pathological conditions or impact inflammatory responses. [9][10][11][12] Various immune cells including macrophages, natural killer cells, dendritic cells, T cells, and regulatory T cells (Treg) are present in the decidua and are required for the proper invasion of trophoblasts during placentation. [9][10][11][12] Various immune cells including macrophages, natural killer cells, dendritic cells, T cells, and regulatory T cells (Treg) are present in the decidua and are required for the proper invasion of trophoblasts during placentation.…”

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confidence: 99%

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Abnormal lymphatic vessel development is associated with decreased decidual regulatory T cells in severe preeclampsia

Jung

Park

Kim

et al. 2018

American J Rep Immunol

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Circulating vascular endothelial growth factor receptor‐3, a pro‐lymphangiogenic and pro‐angiogenic mediator, is decreased in pre‐eclampsia

Palei,

Kaihara,

Cavalli

et al. 2024

Intl J Gynecology & Obste

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ObjectiveTo compare circulating levels of vascular endothelial growth factor receptor 3 (VEGFR‐3) in women with pregnancy‐induced hypertension (PIH) and in non‐pregnant (NP) and healthy pregnant (HP) women.MethodsWe conducted a case–control study including PIH (n = 135), HP (n = 68), and NP (n = 49) women from southeastern Brazil. PIH were diagnosed according to international guidelines, and defined as gestational hypertension (GH, n = 61) or pre‐eclampsia (n = 74). VEGFR‐3 was measured in plasma using ELISA.ResultsPlasma VEGFR‐3 was increased in HP (1207 pg/mL) compared with NP (133 pg/mL) women; however, PIH (729 pg/mL) patients exhibited lower levels than HP women (both p < 0.05). In addition, plasma VEGFR‐3 was decreased in pre‐eclampsia compared with GH (537 versus 980 pg/mL; p < 0.05). When pre‐eclampsia was classified according to different clinical presentations, plasma VEGFR‐3 was further decreased in the cases identified as pre‐eclampsia with severe features, preterm pre‐eclampsia, and pre‐eclampsia accompanied by small for gestational age (all p < 0.05).ConclusionOur data indicate reduced circulating VEGFR‐3 levels in patients with PIH, specifically in those diagnosed with pre‐eclampsia. Moreover, decreased VEGFR‐3 was associated with adverse clinical outcomes in pre‐eclampsia. These findings expand previous evidence of reduced VEGFR‐3 expression in pre‐eclampsia. Future studies should investigate whether it can be used as a predictive biomarker and/or therapeutic target for pre‐eclampsia.

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The defect of both angiogenesis and lymphangiogenesis is involved in preeclampsia

Cited by 32 publications

References 34 publications

Why is placentation abnormal in preeclampsia?

Why is placentation abnormal in preeclampsia?

Abnormal lymphatic vessel development is associated with decreased decidual regulatory T cells in severe preeclampsia

Circulating vascular endothelial growth factor receptor‐3, a pro‐lymphangiogenic and pro‐angiogenic mediator, is decreased in pre‐eclampsia

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