The Complement System and Preeclampsia

Regal, Jean F.; Burwick, Richard M.; Fleming, Sherry D.

doi:10.1007/s11906-017-0784-4

Cited by 78 publications

(66 citation statements)

References 98 publications

(113 reference statements)

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“…Our study is limited in that many other endogenous regulators of complement activation may influence the level of complement activation and were not assessed in the present study (Regal et al. ).…”

Section: Discussionmentioning

confidence: 94%

The complement system in hypertension and renal damage in the Dahl SS rat

et al. 2018

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Evidence indicates the immune system is important in development of hypertension and kidney disease. In the Dahl Salt‐Sensitive (SS) rat model, lymphocytes play a role in development of hypertension and kidney damage after increased sodium intake. Recent transcriptomic analyses demonstrate upregulation of the innate immune complement system in the kidney of Dahl SS rat fed a high‐salt diet, leading us to hypothesize that inhibition of complement activation would attenuate development of hypertension and kidney damage. Male Dahl SS rats on a low salt (0.4% NaCl) diet were instrumented with telemeters for continuous monitoring of arterial blood pressure. Animals received saline vehicle (Control) or sCR1, a soluble form of endogenous Complement Receptor 1 (CR1; CD35) that inhibits complement activation. At Day 0, rats were switched to high salt (4.0% NaCl) diet and assigned to sCR1 (15 mg/kg per day) or Control groups with daily ip injections either days 1–7 or days 14–18. Urine was collected overnight for determination of albumin excretion. Treatment with sCR1, either immediately after high‐salt diet was initiated, or at days 14–18, did not alter development of hypertension or albuminuria. The sCR1 dose effectively inhibited total hemolytic complement activity as well as C3a generation. High salt caused an increase in message for complement regulator Cd59, with minimal change in Crry that controls the C3 convertase. Thus, innate immune complement activation in the circulation is not critical for development of hypertension and kidney damage due to increased sodium intake, and therapeutic manipulation of the complement system is not indicated in salt‐sensitive hypertension.

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Section: Discussionmentioning

confidence: 94%

The complement system in hypertension and renal damage in the Dahl SS rat

et al. 2018

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“…C1q is the core molecule in the classical pathway of complement activation and is widely distributed in the human decidual stroma. [17][18][19][20][21][22][23] Therefore, establishing a normal range of complement components during pregnancy is important for clinical evaluation and research. [8][9][10] Complement factor B (CFB) can bind to C3b to form C3 convertase, promoting activation of the complement system via the alternative pathway, and this process can be inhibited by complement factor H (CFH), an inhibitor of the alternative pathway.…”

Section: Introductionmentioning

confidence: 99%

“…11,12 In general, moderate activation of the complement system is crucial for maintaining pregnancy, and any deviation from normal activation and regulation of the complement system may result in adverse pregnancy outcomes, such as recurrent spontaneous abortion, 13 preterm birth, [14][15][16] and preeclampsia. [17][18][19][20][21][22][23] Therefore, establishing a normal range of complement components during pregnancy is important for clinical evaluation and research. In addition, changes in circulating complement components may provide accessible biomarkers for predicting adverse pregnancy outcomes if "normal" pregnancy components are understood.…”

Section: Introductionmentioning

confidence: 99%

Normal range of complement components during pregnancy: A prospective study

Song

et al. 2019

American J Rep Immunol

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Problem The complement system plays a key role in normal placentation, and delicate regulation of complement system activation is critical for successful pregnancy. Therefore, establishing a normal range of complement components during pregnancy is important for clinical evaluation and research. Methods We performed a prospective study to investigate the normal range of complement components in circulation during different stages of pregnancy. Plasma concentrations of complement factor B (CFB), C1q, complement factor H (CFH), C3, C3c, and C4 were measured using an immunoturbidimetric assay; mannan‐binding lectin (MBL), C3a, C5a, and soluble C5b‐9 (sC5b‐9) levels at different time points of pregnancy were determined by enzyme‐linked immunosorbent assay (ELISA). Results A total of 733 plasma samples were collected from 362 women with a normal pregnancy and 65 samples from non‐pregnant women. In the first trimester of pregnancy, the levels of CFB, CFH, MBL, C3c, C4, and C3a were 414.5 ± 85.9 mg/L (95% CI for mean: 402.4‐426.6 mg/L), 381.0 ± 89.0 mg/L (95% CI for mean: 368.5‐393.6 mg/L), 4274.5 ± 2752 ng/mL (95% CI for mean: 3881.1‐4656.4 ng/mL), 1346.9 ± 419.8 mg/L (95% CI for mean: 1287.7‐1406.0 mg/L), 357.4 ± 101.8 mg/L (95% CI for mean: 343.0‐371.7 mg/L), and 182.5 ± 150.0 ng/mL (95% CI for mean: 186.9‐229.1 ng/mL), respectively. The levels of C3 and C4 increased gradually throughout pregnancy. The levels of C1q, C5a, and sC5b‐9 in the first and second trimesters were nearly the same as those in non‐pregnant women. Conclusion The results of this study show that pregnancy itself may influence the plasma levels of complement system components.

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“…This is coupled with a phenotypic change to a more pro‐inflammatory and pro‐thrombotic state, leading to enhanced vasoconstriction. The role of the immune and complement systems in vascular dysfunction is covered elsewhere …”

Section: Brief Overview Of the Disruption To Vascular Homeostasismentioning

confidence: 99%

Targeting the vascular dysfunction: Potential treatments for preeclampsia

et al. 2019

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Preeclampsia is a pregnancy-specific disorder clinically characterized by new-onset hypertension (>20 weeks' gestation) with one or more of proteinuria and maternal organ dysfunction such as renal insufficiency, liver dysfunction, neurological complications, fetal growth restriction, or uteroplacental dysfunction. 1,2 Each year, preeclampsia is the principal cause of death in over 60 000 women and in more than 500 000 babies globally. 3 The pathophysiological mechanisms underlying the disease are still not entirely clear. Briefly, In 2017, Sarah was awarded her PhD at the University of Melbourne, Australia, and is currently an NHMRC Peter Doherty Research Fellow in the Department of Obstetrics and Gynecology at Monash University, Australia. The focus of her research is to assess the potential of new and old therapeutics to target the vascular dysfunction of preeclampsia, and translate these studies into clinical application. AbstractPreeclampsia is a pregnancy-specific disorder, primarily characterized by new-onset hypertension in combination with a variety of other maternal or fetal signs. The pathophysiological mechanisms underlying the disease are still not entirely clear.Systemic maternal vascular dysfunction underlies the clinical features of preeclampsia. It is a result of oxidative stress and the actions of excessive anti-angiogenic factors, such as soluble fms-like tyrosine kinase, soluble endoglin, and activin A, released by a dysfunctional placenta. The vascular dysfunction then leads to impaired regulation and secretion of relaxation factors and an increase in sensitivity/production of constrictors. This results in a more constricted vasculature rather than the relaxed vasodilated state associated with normal pregnancy. Currently, the only effective "treatment" for preeclampsia is delivery of the placenta and therefore the baby.Often, this means a preterm delivery to save the life of the mother, with all the attendant risks and burdens associated with fetal prematurity. To lessen this burden, there is a pressing need for more effective treatments that target the maternal vascular dysfunction that underlies the hypertension. This review details the vascular effects of key drugs undergoing clinical assessment as potential treatments for women with preeclampsia.

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The Complement System and Preeclampsia

Cited by 78 publications

References 98 publications

The complement system in hypertension and renal damage in the Dahl SS rat

The complement system in hypertension and renal damage in the Dahl SS rat

Normal range of complement components during pregnancy: A prospective study

Targeting the vascular dysfunction: Potential treatments for preeclampsia

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