Imbalance of angiogenic factors and avascular edematous cystic villi in a trisomy 13 pregnancy: A case report

Kakigano, Aiko; Mimura, Kazuya; Kanagawa, Takeshi; Nakayama, Masahiro; Kanayama, Tomoko; Fujita, Satoko; Kinugasa-Taniguchi, Yukiko; Endo, Masayuki; Tomimatsu, Takuji; Kimura, Tadashi

doi:10.1016/j.placenta.2013.04.001

Cited by 13 publications

(11 citation statements)

References 11 publications

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“…In women with trisomy 13, an extra copy of the sFlt-1 gene is associated with increased circulating levels of sFlt-1, reduced PlGF and increased risk of preeclampsia. 150 Several reports have shown higher circulating levels of sFlt-1 in early and late preeclampsia. 116,136–139,149 Serum sFlt-1 is also higher in women with previous preeclampsia (~0.5 ng/mL) than in women with previous normal pregnancy (~0.3 ng/mL), and the increases can be detected even 6 months or more after delivery.…”

Section: Circulating Bioactive Factors and Mmps In Preeclampsiamentioning

confidence: 99%

Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia

Chen

Khalil

2017

Progress in Molecular Biology and Translational Science

230

168

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Normal pregnancy is associated with marked hemodynamic and uterine changes that allow adequate uteroplacental blood flow and uterine expansion for the growing fetus. These pregnancy-associated changes involve significant uteroplacental and vascular remodeling. Matrix metalloproteinases (MMPs) are important regulators of vascular and uterine remodeling. Increases in MMP-2 and MMP-9 have been implicated in vasodilation, placentation and uterine expansion during normal pregnancy. The increases in MMPs could be induced by the increased production of estrogen and progesterone during pregnancy. MMP expression/activity may be altered during complications of pregnancy. Decreased vascular MMP-2 and MMP-9 may lead to decreased vasodilation, increased vasoconstriction, hypertensive pregnancy and preeclampsia. Abnormal expression of uteroplacental integrins, cytokines and MMPs may lead to decreased maternal tolerance, apoptosis of invasive trophoblast cells, inadequate remodeling of spiral arteries, and reduced uterine perfusion pressure (RUPP). RUPP may cause imbalance between the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin and the pro-angiogenic vascular endothelial growth factor and placental growth factor, or stimulate the release of inflammatory cytokines, hypoxia-inducible factor, reactive oxygen species, and angiotensin AT1 receptor agonistic autoantibodies. These circulating factors could target MMPs in the extracellular matrix as well as endothelial and vascular smooth muscle cells, causing generalized vascular dysfunction, increased vasoconstriction and hypertension in pregnancy. MMP activity can also be altered by endogenous tissue inhibitors of metalloproteinases (TIMPs) and changes in the MMP/TIMP ratio. In addition to their vascular effects, decreases in expression/activity of MMP-2 and MMP-9 in the uterus could impede uterine growth and expansion and lead to premature labor. Understanding the role of MMPs in uteroplacental and vascular remodeling and function could help design new approaches for prediction and management of preeclampsia and premature labor.

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Section: Circulating Bioactive Factors and Mmps In Preeclampsiamentioning

confidence: 99%

Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia

Chen

Khalil

2017

Progress in Molecular Biology and Translational Science

230

168

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“…In PE, the increase in sFlt-1 and decrease PlGF occur at more pronounced levels than those seen in Norm-Preg women (Jardim et al, 2015). sFlt-1 gene is localized on chromossome 13q12, and an extra copy of this gene in women with trisomy 13 may lead to excess circulating sFlt-1, reduced PlGF and increased risk of PE (Kakigano et al, 2013). Several reports have shown higher circulating levels of sFlt-1 in early and late PE (Tsatsaris et al, 2003; Ramma et al, 2012; Bian et al, 2015; March et al, 2015; Molvarec et al, 2015; Tuzcu et al, 2015).…”

Section: Circulating Bioactive Factors In Preeclampsiamentioning

confidence: 99%

Mechanisms of Endothelial Dysfunction in Hypertensive Pregnancy and Preeclampsia

Possomato-Vieira

Khalil

2016

Advances in Pharmacology

185

117

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Preeclampsia is a pregnancy-related disorder characterized by hypertension, and could lead to maternal and fetal morbidity and mortality. Although the causative factors and pathophysiological mechanisms are unclear, endothelial dysfunction is a major hallmark of preeclampsia. Clinical tests and experimental research have suggested that generalized endotheliosis in the systemic, renal, cerebral and hepatic circulation could decrease endothelium-derived vasodilators such as nitric oxide, prostacyclin and hyperpolarization factor and increase vasoconstrictors such as endothelin-1 and thromboxane A2, leading to increased vasoconstriction, hypertension and other manifestation of preeclampsia. In search for the upstream mechanisms that could cause endothelial dysfunction, certain genetic, demographic and environmental risk factors have been suggested to cause abnormal expression of uteroplacental integrins, cytokines and matrix metalloproteinases, leading to decreased maternal tolerance, apoptosis of invasive trophoblast cells, inadequate spiral arteries remodeling, reduced uterine perfusion pressure (RUPP), and placental ischemia/hypoxia. RUPP may cause imbalance between the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin and the pro-angiogenic factors vascular endothelial growth factor and placental growth factor, or stimulate the release of other circulating bioactive factors such as inflammatory cytokines, hypoxia-inducible factor-1, reactive oxygen species, and angiotensin AT1 receptor agonistic autoantibodies. These circulating factors could then target endothelial cells and cause generalized endothelial dysfunction. Therapeutic options are currently limited, but understanding the factors involved in endothelial dysfunction could help design new approaches for prediction and management of preeclampsia.

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“…The sFlt‐1 gene has a gene locus on chromosome 13q12. In women with trisomy 13, an extra copy of the sFlt‐1 gene is associated with increased circulating sFlt‐1, reduced PlGF and increased risk of PE . Studies have shown higher circulating levels of sFlt‐1 in early and late PE .…”

Section: Circulating Bioactive Factors In Pementioning

confidence: 99%

Molecular determinants of microvascular dysfunction in hypertensive pregnancy and preeclampsia

Gao

Rong

et al. 2018

Microcirculation

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Preeclampsia is a pregnancy-related disorder characterized by hypertension and often fetal intrauterine growth restriction, but the underlying mechanisms are unclear. Defective placentation and apoptosis of invasive cytotrophoblasts cause inadequate remodeling of spiral arteries, placental ischemia, and reduced uterine perfusion pressure (RUPP). RUPP causes imbalance between the anti-angiogenic factors soluble fms-like tyrosine kinase-1 and soluble endoglin and the pro-angiogenic vascular endothelial growth factor and placental growth factor, and stimulates the release of proinflammatory cytokines, hypoxia-inducible factor, reactive oxygen species, and angiotensin AT 1 receptor agonistic autoantibodies. These circulating factors target the vascular endothelium, smooth muscle and various components of the extracellular matrix. Generalized endotheliosis in systemic, renal, cerebral, and hepatic vessels causes decreases in endothelium-derived vasodilators such as nitric oxide, prostacyclin and hyperpolarization factor, and increases in vasoconstrictors such as endothelin-1 and thromboxane A2. Enhanced mechanisms of vascular smooth muscle contraction, such as intracellular Ca 2+ , protein kinase C, and Rho-kinase cause further increases in vasoconstriction. Changes in matrix metalloproteinases and extracellular matrix cause inadequate vascular remodeling and increased arterial stiffening, leading to further increases in vascular resistance and hypertension.Therapeutic options are currently limited, but understanding the molecular determinants of microvascular dysfunction could help in the design of new approaches for the prediction and management of preeclampsia. K E Y W O R D S endothelium, extracellular matrix, microvessels, placental ischemia, vascular smooth muscle | 3 of 25 YU et al. to microvascular dysfunction, decreased vascular relaxation, increased vasoconstriction, aberrant vascular remodeling, and HTN.Throughout the review we will briefly define the factor involved, and describe the levels during normal pregnancy followed by the changes in human PE and experimental HTN-Preg. We will then discuss how identifying the molecular determinant of microvascular dysfunction could help design new approaches in the prediction and management of PE. | DEFEC TIVE PL ACENTATI ON AND UTEROPL ACENTAL ISCHEMIA IN PEDuring early pregnancy, the placenta is developed as a maternalfetal interface through several biological processes including vasculogenesis, angiogenesis, and trophoblast invasion and remodeling of spiral arteries. Vasculogenesis is the development of de novo blood vessels from endothelial progenitor cells and occurs ~18-35 days after conception in humans. Angiogenesis is the sprouting of new blood vessels from preexisting vessels and is regulated by the coordinated actions of proangiogenic factors and the invasive capability of trophoblast cells. 12 Healthy pregnancy requires adequate placental vascularization. During the first trimester, the placental extravillous trophoblasts invade deep into the maternal de...

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Imbalance of angiogenic factors and avascular edematous cystic villi in a trisomy 13 pregnancy: A case report

Cited by 13 publications

References 11 publications

Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia

Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia

Mechanisms of Endothelial Dysfunction in Hypertensive Pregnancy and Preeclampsia

Molecular determinants of microvascular dysfunction in hypertensive pregnancy and preeclampsia

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