Gestational angiogenic biomarker patterns in high risk preeclampsia groups

Maynard, Sharon E.; Crawford, Sybil L.; Bathgate, Susanne L.; Yan, Jing; Robidoux, Laura; Moore, Melissa J.; Simas, Tiffany A. Moore

doi:10.1016/j.ajog.2013.03.017

Cited by 43 publications

(30 citation statements)

References 31 publications

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“…This supports the hypothesis that subset-specific disease pathways result in the final common symptom complex or disease recognized as preeclampsia. In keeping with the present results are those of Maynard et al 6 who found that 3 angiogenic markers (PlGF, sFlt-1, endoglin) differed in a prospectively-collected high-risk cohort of women with chronic hypertension, multiple gestation, insulin-dependent diabetes, or previous preeclampsia compared with low-risk controls. Their study focused on changes in angiogenic markers over time, and complements our results by demonstrating different longitudinal patterns of angiogenic biomarkers among high-risk groups.…”

Section: Commentsupporting

confidence: 92%

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Preeclampsia in high risk women is characterized by risk group-specific abnormalities in serum biomarkers

Metz

Allshouse

Euser

et al. 2014

American Journal of Obstetrics and Gynecology

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OBJECTIVE To determine if early pregnancy serum biomarkers in high-risk women who develop preeclampsia vary according to risk factor. STUDY DESIGN We performed a secondary analysis of the Maternal-Fetal Medicine Units Network randomized controlled trial of low-dose aspirin for the prevention of preeclampsia in high-risk women. Serum biomarker levels at enrollment (before initiation of aspirin or placebo) were compared between women who did and did not develop preeclampsia, both for the group as a whole and within each of 4 high-risk groups (insulin-dependent diabetes, hypertension, multiple gestation, and previous preeclampsia) using a regression model adjusting for gestational age at collection and prepregnancy body mass index. RESULTS 1258 women were included (233 with insulin-dependent diabetes, 387 with chronic hypertension, 315 with a multiple gestation, 323 with previous preeclampsia). Multiple early pregnancy serum biomarkers differed between women who did and did not develop preeclampsia. Each high-risk group had a unique and largely nonoverlapping pattern of biomarker abnormality. Differences between those who did and did not develop preeclampsia were noted in vascular cell adhesion molecule in the diabetes group; human chorionic gonadotropin, soluble tumor necrosis factor receptor-2, tumor necrosis factor-alpha, selectin and angiogenin in the chronic hypertension group; interleukin-6, placental growth factor, soluble fms-like tyrosine kinase plus endoglin to placental growth factor ratio in the multiple gestation group; and angiogenin in the previous preeclampsia group. CONCLUSION Patterns of serum biomarkers vary by high-risk group. These data support the hypothesis that multiple pathogenic pathways lead to the disease recognized clinically as preeclampsia.

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Section: Commentsupporting

confidence: 92%

“…5,6 We therefore hypothesized that the ability of biomarkers to predict the occurrence of preeclampsia would vary among high-risk subgroups (insulin-dependent diabetes, hypertension, multiple gestation. or previous preeclampsia).…”

mentioning

confidence: 99%

Preeclampsia in high risk women is characterized by risk group-specific abnormalities in serum biomarkers

Metz

Allshouse

Euser

et al. 2014

American Journal of Obstetrics and Gynecology

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“…IgG from patients with venous thrombosis (VT+/PM+ and VT+/PM−) induced significantly higher levels of sFlt-1 compared to VT−/PM+ APS patients while IgG from APS patients with isolated pregnancy morbidity (VT−/PM+) induced significantly higher levels of sEng [94]. Both factors have been associated with poor placentation, uteroplacental hypoperfusion, fetal hypoxia, and pre-eclampsia [95].…”

Section: Cellular Activation Translates To Clinical Manifestationsmentioning

confidence: 96%

The Journey of Antiphospholipid Antibodies From Cellular Activation to Antiphospholipid Syndrome

González

Brasier

2015

Curr Rheumatol Rep

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Pathogenic antiphospholipid antibodies (aPL) are the driving factors of recurrent pregnancy loss and thrombosis that characterize antiphospholipid syndrome (APS). Current evidence indicates that aPL induce a procoagulant phenotype in the vasculature and abnormal cellular proliferation and differentiation in placental tissues to cause the typical clinical features; however, the molecular mechanisms underlying these processes remain incompletely understood. Inflammation serves as a necessary link between the observed procoagulant phenotype and actual thrombus development and is an important mediator of the placental injury in APS patients. However, the underlying mechanisms for these events have also not been fully elucidated. In this review, we will outline the available data that give us our current understanding of the pathophysiology of APS, especially as it relates to the development of thromboembolic and obstetric pathological phenomena in these patients. We will also describe the intracellular signaling pathways activated by aPL in various cellular subtypes and outline the current evidence linking these pathways to clinical phenotypes. Finally, we will discuss the implications of distinct molecular patterns defining clinical phenotypes of APS patients.

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“…Uteroplacental ischemia can lead to the production of anti-angiogenic factors [103–113], such as sFlt-1 (soluble fms-like tyrosine kinase-1) [114–117] and endoglin [69,118], which can induce endothelial dysfunction and predispose to preeclampsia or an anti-angiogenic state [57,119–129]. In addition, an excess production of trophoblast debris can result in exaggerated intravascular inflammation and endothelial cell dysfunction [130–134].…”

Section: Commentmentioning

confidence: 99%

Failure of physiologic transformation of spiral arteries, endothelial and trophoblast cell activation, and acute atherosis in the basal plate of the placenta

Labarrere

DiCarlo

Bammerlin

et al. 2017

American Journal of Obstetrics and Gynecology

130

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Background Failure of physiologic transformation of spiral arteries has been reported in preeclampsia, fetal growth restriction, fetal death, and spontaneous preterm labor with intact or ruptured membranes. Spiral arteries with failure of physiologic transformation are prone to develop atherosclerotic-like lesions of atherosis. There are striking parallels between preeclampsia and atherosclerotic disease, and between lesions of atherosis and atherosclerosis. Endothelial activation, identified by intercellular adhesion molecule-1 expression, is present in atherosclerotic-like lesions of heart transplantation and considered a manifestation of rejection. Similarly, endothelial activation/dysfunction has been implicated in the pathophysiology of atherosclerosis and preeclampsia. Intercellular adhesion molecule-1-overexpressing-activated endothelial cells are more resistant to trophoblast displacement than nonactivated endothelium and may contribute to shallow spiral artery trophoblastic invasion in obstetrical syndromes having failure of physiologic transformation. Objective To determine whether failure of spiral artery physiologic transformation was associated with activation of interstitial extravillous trophoblasts and/or spiral artery endothelium and presence of acute atherosis in the placental basal plate. Study Design A cross-sectional study of 123 placentas (19-42 weeks’ gestation) obtained from normal pregnancies (n = 22), preterm prelabor rupture of membranes (n = 26), preterm labor (n = 23), preeclampsia (n = 27), intrauterine fetal death (n = 15), and small for gestational age (n = 10) was performed. Failure of spiral artery physiologic transformation and presence of cell activation was determined using immunohistochemistry of placental basal plates containing a median of 4 (minimum: 1; maximum: 9) vessels per placenta. Endothelial/trophoblast cell activation was defined by the expression of intercellular adhesion molecule-1 (ICAM-1). Investigators examining microscopic sections were blinded to clinical diagnosis. Pairwise comparisons among placenta groups were performed with the Fisher’s exact and Wilcoxon rank sum tests using a Bonferroni-adjusted level of significance (.025). Results 87% (94/108) of placentas having spiral arteries with failure of physiologic transformation (actin-positive and cytokeratin-negative) in the basal plate, and 0% (0/15) of placentas having only spiral arteries with complete physiologic transformation (cytokeratin-positive and actin-negative), had arterial endothelial and/or interstitial extravillous trophoblasts reactive with the ICAM-1 activation marker (P < .001). A significant correlation (R2 = 0.84) was found between expression of spiral artery endothelial and interstitial extravillous trophoblast ICAM-1 (P < .001) in activated placentas. Lesions of atherosis were found in 31.9% (30/94) of placentas with complete and/or partial failure of physiologic transformation of spiral arteries that were ICAM-1-positive, in none of the 14 placentas with failure of physiolog...

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Gestational angiogenic biomarker patterns in high risk preeclampsia groups

Cited by 43 publications

References 31 publications

Preeclampsia in high risk women is characterized by risk group-specific abnormalities in serum biomarkers

Preeclampsia in high risk women is characterized by risk group-specific abnormalities in serum biomarkers

The Journey of Antiphospholipid Antibodies From Cellular Activation to Antiphospholipid Syndrome

Failure of physiologic transformation of spiral arteries, endothelial and trophoblast cell activation, and acute atherosis in the basal plate of the placenta

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