Reconciling the distinct roles of angiogenic/anti-angiogenic factors in the placenta and maternal circulation of normal and pathological pregnancies

Umapathy, Anandita; Chamley, Lawrence W.; James, Joanna L.

doi:10.1007/s10456-019-09694-w

Cited by 100 publications

(66 citation statements)

References 113 publications

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“…Many other vasoactive and immunological mediators have been studied in the maternal serum for the diagnosis or prediction of PE, and are summarized in Table 3 . It is generally accepted that the placenta is the primary source of these factors and is therefore the key driver of the global functioning of the maternal circulation [ 81 ]. However, it should be emphasized that abnormal serum concentrations of many of these factors have also been documented in nonpregnant individuals with (preclinical) chronic cardiovascular and/or renal disease ( Table 3 ).…”

Section: Pathophysiologymentioning

confidence: 99%

Preeclampsia Is a Syndrome with a Cascade of Pathophysiologic Events

Gyselaers

2020

JCM

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This review integrates the currently available information on the molecular, cellular, and systemic mechanisms involved in the pathophysiology of preeclampsia. It highlights that the growth, protection, and promotion of the conceptus requires the modulation of an intact maternal immune system, communication between the mother and fetus, and adaptation of the maternal organic functions. A malfunction in any of these factors, on either side, will result in a failure of the cascade of events required for the normal course of pregnancy. Maladaptive processes, initially aiming to protect the conceptus, fail to anticipate the gradually increasing cardiovascular volume load during the course of pregnancy. As a result, multiple organ dysfunctions install progressively and eventually reach a state where mother and/or fetus are at risk of severe morbidity or even mortality, and where the termination of pregnancy becomes the least harmful solution. The helicopter view on pathophysiologic processes associated with preeclampsia, as presented in this paper, illustrates that the etiology of preeclampsia cannot be reduced to one single mechanism, but is to be considered a cascade of consecutive events, fundamentally not unique to pregnancy.

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Section: Pathophysiologymentioning

confidence: 99%

Preeclampsia Is a Syndrome with a Cascade of Pathophysiologic Events

Gyselaers

2020

JCM

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“…Their release into the maternal circulation contributes to the adaptation of the maternal cardiovascular system to pregnancy. Many issues in this field such as assay methodology and lack of data considering different placental cell types mean that the physiological roles of these factors in the maternal and placental circulations are making them a misnomer [23].…”

Section: Ratio Sflt-1 /Pigfmentioning

confidence: 99%

Expression of PIGF and sFLT-1 Biomarkers in Pregnancy Toxaemia

Mihălceanu¹,

Scripcariu²,

Lazar³

et al. 2020

Rev. Chim.

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Toxaemia is a pathological condition specific to the period of pregnancy which begins and is indissolubly related to the presence of placenta. Antiangiogenic factors, such as sFLT-1 (soluble tyrosine kinase receptor fms-like) and sEng (soluble endoglin) play an important role in the first part of pregnancy. They are linked to physiological vascular neoformation, and, in the second part of the pregnancy, grant the endothelial functionality and physiological vascular remodeling. The aim of the study is to try to establish the levels of the sFLT-1/PIGF ratio, as a prognostic tool in the patient with pre-eclampsia, depending on the influence of the cumulative risk factors. The sFLT-1 / PIGF report is a potential prognostic parameter in monitoring preeclampsia. The results of our study confirm the importance of deterring these markers for the diagnosis and monitoring of hypertensive pregnancies and at the same time to emphasize that the sFLT-1/PIGF ratio is a good predictor of preeclampsia Keywords: pregnancy, antiangiogenic factors, toxaemiaToxaemia is a pathological condition specific to the period of pregnancy which begins and is indissolubly related to the presence of placenta. The diseases is a multisystemic disorder, implying an increased incidence of morbidity and mortality for both the mother and the foetus[1].This condition starts even in the absence of the foetus (as is the case of the mola hydatiforme) and the symptoms usually dissapear at the time of delivery of the placenta. Toxaemia is a condition that begins at the placenta and ends in the maternal endothelium, being characterized by generalized endothelial dysfunction and affecting all susceptible vascular vessels from kidneys, central nervous system, liver to placenta [2][3][4].Antiangiogenic factors, such as sFLT-1 (soluble tyrosine kinase receptor fms-like) and sEng (soluble endoglin) play an important role in the first part of pregnancy. They are linked to physiological vascular neoformation, and, in the second part of the pregnancy, grant the endothelial functionality and physiological vascular remodeling. Soluble FLT-1 is a circulating anti-angiogenic protein that binds to the receptor of the PIGF and VEGF, thus preventing interaction with endothelial receptors, causing endothelial dysfunction. Endoglin is a surface co-receptor protein of TGF (transformig growth factor) β1 and β3 [5].The sEng factor is its soluble form, a novel anti-angiogenic factor that acts in synergy with sFLT-1. In normal pregnancy, a proangiogenic status appears, with low levels of sFLT-1 and increased levels of PIGF, by the end of the second trimester. Towards the end of the pregnancy these levels return to normal. In pregnant women with toxaemia, angiogenic profile abnormalities appear, with early changes in the prevalence of anti-angiogenic status leading to endothelial dysfunction. Thus PIGF and VEGF levels are lower than normal, and sFLT-1 and sEng levels are increased. sFLT-1 released from the placental circulation in large quantities will destroy the homeostasis of t...

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“…Th1 cells, NK cells, and self-reactive B cells stimulate the inflammatory response through cytokines activity, which results in an inappropriate trophoblast invasion and impaired spiral artery remodeling in early pregnancy [ 17 , 18 ]. Uteroplacental underperfusion is therefore the cause of placental ischemia which triggers oxidative-inflammation cascade and increases production of antiangiogenic factors: soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng) [ 19 – 21 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of Inflammation in the Pathogenesis of Preeclampsia

Michalczyk

Celewicz

et al. 2020

Mediators of Inflammation

109

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Preeclampsia (PE) affects 5-8% of pregnant women, and it is the major cause of perinatal morbidity and mortality. It is defined as arterial hypertension in women after 20 weeks of gestation which cooccurs with proteinuria (300 mg/d) or as arterial hypertension which is accompanied by one of the following: renal failure, liver dysfunction, hematological or neurological abnormalities, intrauterine growth restriction, or uteroplacental insufficiency. Currently, pathophysiology of preeclampsia poses a considerable challenge for perinatology. Preeclampsia is characterized by excessive and progressive activation of the immune system along with an increase in proinflammatory cytokines and antiangiogenic factors in fetoplacental unit as well as in vascular endothelium in pregnant women. A single, major underlying mechanism of preeclampsia is yet to be identified. This paper discusses the current understanding of the mechanisms which underlie the development of the condition. Some significant factors responsible for PE development include oxidative stress, abnormal concentration and activity in mononuclear phagocytic system, altered levels of angiogenic and antiangiogenic factors, and impaired inflammatory response triggered by inflammasomes. Detailed understanding of pathophysiology of inflammatory process in PE can largely contribute to new, targeted anti-inflammatory therapies that may improve perinatal outcomes in PE patients.

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Reconciling the distinct roles of angiogenic/anti-angiogenic factors in the placenta and maternal circulation of normal and pathological pregnancies

Cited by 100 publications

References 113 publications

Preeclampsia Is a Syndrome with a Cascade of Pathophysiologic Events

Preeclampsia Is a Syndrome with a Cascade of Pathophysiologic Events

Expression of PIGF and sFLT-1 Biomarkers in Pregnancy Toxaemia

The Role of Inflammation in the Pathogenesis of Preeclampsia

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