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American Journal of Obstetrics and... Feb 2022Preeclampsia is a disease whose characterization has not changed in the 150 years since the cluster of signs associated with the disorder were first described. Although... (Review)
Review
Preeclampsia is a disease whose characterization has not changed in the 150 years since the cluster of signs associated with the disorder were first described. Although our understanding of the pathophysiology of preeclampsia has advanced considerably since then, there is still little consensus regarding the true etiology of preeclampsia. As a consequence, preeclampsia has earned the moniker "disease of theories," predominantly because the underlying biological mechanisms linking clinical epidemiologic findings to observed organ dysfunction in preeclampsia are far from clear. Despite the lack of cohesive evidence, expert consensus favors the hypothesis that preeclampsia is a primary placental disorder. However, there is now emerging evidence that suboptimal maternal cardiovascular performance resulting in uteroplacental hypoperfusion is more likely to be the cause of secondary placental dysfunction in preeclampsia. Preeclampsia and cardiovascular disease share the same risk factors, preexisting cardiovascular disease is the strongest risk factor (chronic hypertension, congenital heart disease) for developing preeclampsia, and there are now abundant data from maternal echocardiography and angiogenic marker studies that cardiovascular dysfunction precedes the development of preeclampsia by several weeks or months. Importantly, cardiovascular signs and symptoms (hypertension, cerebral edema, cardiac dysfunction) predominate in preeclampsia at clinical presentation and persist into the postnatal period with a 30% risk of chronic hypertension in the decade after birth. Placental malperfusion caused by suboptimal maternal cardiovascular performance may lead to preeclampsia, thereby explaining the preponderance of cardiovascular drugs (aspirin, calcium, statins, metformin, and antihypertensives) in preeclampsia prevention strategies. Despite the seriousness of the maternal and fetal consequences, we are still developing sensitive screening, reliable diagnostic, effective therapeutic, or improvement strategies for postpartum maternal cardiovascular legacy in preeclampsia. The latter will only become clear with an acceptance and understanding of the cardiovascular etiology of preeclampsia.
Topics: Cardiovascular Diseases; Female; Humans; Parity; Placenta; Placental Circulation; Placentation; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Vascular Resistance
PubMed: 33771361
DOI: 10.1016/j.ajog.2020.10.024 -
Obstetrics and Gynecology Clinics of... Jun 2018Hypertensive disorders of pregnancy are a heterogeneous group of conditions that include chronic hypertension, gestational hypertension, preeclampsia, and preeclampsia... (Review)
Review
Hypertensive disorders of pregnancy are a heterogeneous group of conditions that include chronic hypertension, gestational hypertension, preeclampsia, and preeclampsia superimposed on chronic hypertension. These disorders account for a significant proportion of perinatal morbidity and mortality nearly 10% of all maternal deaths in the United States. Given the substantial health burden of hypertensive disorders in pregnancy, there is increasing interest in optimizing management of these conditions. This article summarizes the diagnosis and management of each of the disorders in the spectrum of hypertension in pregnancy and highlights recent updates in the field.
Topics: Chronic Disease; Eclampsia; Female; Humans; Hypertension; Hypertension, Pregnancy-Induced; Pre-Eclampsia; Pregnancy; Risk Factors
PubMed: 29747734
DOI: 10.1016/j.ogc.2018.01.012 -
The American Journal of Emergency... Aug 2022Eclampsia is a rare partum and puerperal condition that carries a high rate of morbidity and mortality. (Review)
Review
INTRODUCTION
Eclampsia is a rare partum and puerperal condition that carries a high rate of morbidity and mortality.
OBJECTIVE
This review highlights the pearls and pitfalls of the care of patients with eclampsia, including presentation, evaluation, and evidence-based management in the emergency department (ED).
DISCUSSION
Eclampsia is a hypertensive disease of pregnancy defined by new onset tonic-clonic, focal, or multifocal seizures or unexplained altered mental status in a pregnant or postpartum patient in the absence of other causative etiologies. However, signs and symptoms of preeclampsia and prodromes of eclampsia are often subtle and non-specific, making the diagnosis difficult. Thus, it should be considered in pregnant and postpartum patients who present to the ED. Laboratory testing including complete blood cell count, renal and liver function panels, electrolytes, glucose, coagulation panel, fibrinogen, lactate dehydrogenase, uric acid, and urinalysis, as well as imaging to include head computed tomography, can assist, but these evaluations should not delay management. Components of treatment include emergent obstetric specialist consultation, magnesium administration, and blood pressure control in patients with hypertension. Definitive treatment of eclampsia requires emergent delivery in pregnant patients. If consultants are not in-house, emergent stabilization and immediate transfer are required.
CONCLUSIONS
An understanding of eclampsia can assist emergency clinicians in rapid recognition and timely management of this potentially deadly disease.
Topics: Eclampsia; Female; Humans; Hypertension; Postpartum Period; Pre-Eclampsia; Pregnancy; Prevalence; Seizures
PubMed: 35716535
DOI: 10.1016/j.ajem.2022.06.004 -
Frontiers in Immunology 2022Preeclampsia is a common and serious complication of pregnancy, posing a threat to maternal and fetal safety due to the lack of effective biomarkers and treatment...
OBJECTIVE
Preeclampsia is a common and serious complication of pregnancy, posing a threat to maternal and fetal safety due to the lack of effective biomarkers and treatment strategies. This study aimed to identify potential biomarkers that can be used to predict preeclampsia and identify the molecular mechanisms of preeclampsia pathogenesis and drug prediction at the transcriptome level.
METHODS
We analyzed differential expression genes (DEGs) in preeclampsia and non-preeclampsia groups in the GSE75010 dataset, cross-linking with extracted inflammatory response-related genes to obtain differentially expressed inflammation-related genes (DINRGs). Enrichment analysis and protein-protein interaction (PPI) networks were constructed to understand the functions and enrichment pathways. Machine learning models were used to identify key genes associated with preeclampsia and build a nomogram in the training set, which was validated in the validation set. The R package RcisTarget was used to predict transcription factors, and Cytoscape was used to construct miRNA-mRNA pathways, which could identify the molecular mechanisms. Then, we conducted molecular docking of the obtained key genes (inhibin subunit beta A), (opioid receptor kappa 1), and (trophoblast glycoprotein), as well as predicted transcription factors with drug molecules. Additionally, the CIBERSORT method explored the differences in immune cell infiltration between preeclampsia and non-preeclampsia samples based on the GSE75010 dataset.
RESULTS
A total of 69 DINRGs associated with preeclampsia patients were screened. , and were the key genes based on machine learning models. A nomogram for prediction was further constructed, and the receiver operating curves (ROCs) showed good performance. Based on the transcriptome level of key genes, we proposed that RELA-miR-548K/miR-1206-TPBG may be a potential RNA regulatory pathway regulating the progression of early preeclampsia. Molecular docking suggested the effectiveness of curcumin in the treatment of preeclampsia. Additionally, regulatory T cells (Tregs) and resting mast cells were significantly different between the two groups.
CONCLUSION
In summary, we identified three key inflammation-associated genes, namely , and , which can be used as potential genetic biomarkers for preeclampsia prediction and treatment, and established a nomogram as a predictive model. Additionally, we provided insights into the mechanisms of preeclampsia development at the transcriptome level and performed corresponding drug predictions.
Topics: Female; Gene Regulatory Networks; Genetic Markers; Humans; Inflammation; MicroRNAs; Molecular Docking Simulation; Pre-Eclampsia; Pregnancy; Transcription Factors
PubMed: 35880174
DOI: 10.3389/fimmu.2022.883404 -
Nature Reviews. Disease Primers Feb 2023
Topics: Pregnancy; Female; Humans; Pre-Eclampsia
PubMed: 36797280
DOI: 10.1038/s41572-023-00425-6 -
Hypertension (Dallas, Tex. : 1979) Jun 2020Preeclampsia is a common pregnancy complication, affecting 2% to 8% of pregnancies worldwide, and is an important cause of both maternal and fetal morbidity and... (Review)
Review
Preeclampsia is a common pregnancy complication, affecting 2% to 8% of pregnancies worldwide, and is an important cause of both maternal and fetal morbidity and mortality. Importantly, although aspirin and calcium are able to prevent preeclampsia in some women, there is no cure apart from delivery of the placenta and fetus, often necessitating iatrogenic preterm birth. Preclinical models of preeclampsia are widely used to investigate the causes and consequences of preeclampsia and to evaluate safety and efficacy of potential preventative and therapeutic interventions. In this review, we provide a summary of the published preclinical models of preeclampsia that meet human diagnostic criteria, including the development of maternal hypertension, together with new-onset proteinuria, maternal organ dysfunction, and uteroplacental dysfunction. We then discuss evidence from preclinical models for multiple causal factors of preeclampsia, including those implicated in early-onset and late-onset preeclampsia. Next, we discuss the impact of exposure to a preeclampsia-like environment for later maternal and progeny health. The presence of long-term impairment, particularly cardiovascular outcomes, in mothers and progeny after an experimentally induced preeclampsia-like pregnancy, implies that later onset or reduced severity of preeclampsia will improve later maternal and progeny health. Finally, we summarize published intervention studies in preclinical models and identify gaps in knowledge that we consider should be targets for future research.
Topics: Animals; Disease Models, Animal; Female; Pre-Eclampsia; Pregnancy
PubMed: 32248704
DOI: 10.1161/HYPERTENSIONAHA.119.14598 -
American Journal of Obstetrics and... Feb 2022Animal models have been critical in investigating the pathogenesis, mediators, and even therapeutic options for a number of diseases, including preeclampsia.... (Review)
Review
Animal models have been critical in investigating the pathogenesis, mediators, and even therapeutic options for a number of diseases, including preeclampsia. Preeclampsia is the leading cause of maternal and fetal morbidity and mortality worldwide. The placenta is thought to play a central role in the pathogenesis of this disease because it releases antiangiogenic and proinflammatory factors into the maternal circulation, resulting in the maternal syndrome. Despite the deleterious effects preeclampsia has been shown to have on the mother and baby during pregnancy and postpartum, there is still no effective treatment for this disease. Although clinical studies in patients are crucial to identify the involvement of pathogenic factors in preeclampsia, there are obvious limitations that prevent detailed investigation of the quantitative importance of time-dependent mechanisms involved in this syndrome. Animal models allow investigators to perform proof-of-concept studies and examine whether certain factors found in women with preeclampsia mediate hypertension and other manifestations of this disease. In this brief review, we summarize some of the more widely studied models used to investigate pathophysiological mechanisms that are thought to be involved in preeclampsia. These include models of placental ischemia, angiogenic imbalance, and maternal immune activation. Infusion of preeclampsia-related factors into animals has been widely studied to understand the specific mediators of this disease. These models have been included, in addition to a number of genetic models involved in overexpression of the renin-angiotensin system, complement activation, and trophoblast differentiation. Together, these models cover multiple mechanisms of preeclampsia from trophoblast dysfunction and impaired placental vascularization to the excess circulating placental factors and clinical manifestation of this disease. Most animal studies have been performed in rats and mice; however, we have also incorporated nonhuman primate models in this review. Preclinical animal models not only have been instrumental in understanding the pathophysiology of preeclampsia but also continue to be important tools in the search for novel therapeutic options for the treatment of this disease.
Topics: Animals; Disease Models, Animal; Female; Models, Genetic; Pre-Eclampsia; Pregnancy
PubMed: 33722383
DOI: 10.1016/j.ajog.2020.10.025 -
International Journal of Molecular... Aug 2019Preeclampsia, a systemic vascular disorder characterized by new-onset hypertension and proteinuria after 20 weeks of gestation, is the leading cause of maternal and... (Review)
Review
Preeclampsia, a systemic vascular disorder characterized by new-onset hypertension and proteinuria after 20 weeks of gestation, is the leading cause of maternal and perinatal morbidity and mortality. Maternal endothelial dysfunction caused by placental factors has long been accepted with respect to the pathophysiology of preeclampsia. Over the past decade, increased production of placental antiangiogenic factors has been identified as a placental factor leading to maternal endothelial dysfunction and systemic vascular dysfunction. This review summarizes the recent advances in understanding the molecular mechanisms of endothelial dysfunction caused by placental antiangiogenic factors, and the novel clinical strategies based on these discoveries.
Topics: Angiogenesis Inhibitors; Endothelium, Vascular; Female; Humans; Placenta; Pre-Eclampsia; Pregnancy; Risk Factors; Vascular Endothelial Growth Factor A
PubMed: 31480243
DOI: 10.3390/ijms20174246 -
MicroRNA (Shariqah, United Arab... 2019Preeclampsia (PE) continues to represent a worldwide problem and challenge for both clinicians and laboratory-based doctors. Despite many efforts, the knowledge acquired... (Review)
Review
Preeclampsia (PE) continues to represent a worldwide problem and challenge for both clinicians and laboratory-based doctors. Despite many efforts, the knowledge acquired regarding its pathogenesis and pathophysiology does not allow us to treat it efficiently. It is not possible to arrest its progressive nature, and the available therapies are limited to symptomatic treatment. Furthermore, both the diagnosis and prognosis are frequently uncertain, whilst the ability to predict its occurrence is very limited. MicroRNAs are small non-coding RNAs discovered two decades ago, and present great interest given their ability to regulate almost every aspect of the cell function. A lot of evidence regarding the role of miRNAs in pre-eclampsia has been accumulated in the last 10 years. Differentially expressed miRNAs are characteristic of both mild and severe PE. In many cases they target signaling pathway-related genes that result in altered processes which are directly involved in PE. Immune system, angiogenesis and trophoblast proliferation and invasion, all fundamental aspects of placentation, are controlled in various degrees by miRNAs which are up- or downregulated. Finally, miRNAs represent a potential therapeutic target and a diagnostic tool.
Topics: Animals; Female; Humans; MicroRNAs; Pre-Eclampsia; Pregnancy; Trophoblasts
PubMed: 30101723
DOI: 10.2174/2211536607666180813123303 -
Circulation Aug 2021
Topics: Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pre-Eclampsia; Pregnancy
PubMed: 34460319
DOI: 10.1161/CIRCULATIONAHA.121.056140