REVIEW

CURRENT
OPINION Pathogenesis of preeclampsia
Monica Sircar a, Ravi Thadhani a, and S. Ananth Karumanchi b

Purpose of review
Preeclampsia is a gestational kidney disease characterized by glomerular endothelial injury, leading to
maternal hypertension and proteinuria. If not addressed promptly, there is significant maternal and fetal
morbidity and mortality. When severe, this disorder can cause hepatic and neurologic dysfunction.
Understandably, this placental disease enters the focus of the obstetrician first; however, with progression,
the nephrologist can also be enlisted. Typical complications include acute kidney injury, refractory
hypertension, and acute pulmonary edema. This review summarizes recent literature on the pathogenesis of
this condition and will highlight new diagnostic and therapeutic options for preeclampsia.
Recent findings
Over the past decade, the role of soluble vascular factors in preeclampsia has shed light on the mechanism
underlying this disease. During the last 2 years, several new therapeutics have been developed that target
implicated circulating angiogenic factors, including soluble fms-like tyrosine kinase 1, an endogenous
vascular endothelial growth factor inhibitor. Serum levels of angiogenic factors have been correlated with a
constellation of hemodynamic and pathophysiologic changes. Thus, circulating levels of these factors may
serve both diagnostic and prognostic purposes.
Summary
Overall, our understanding of preeclampsia has developed significantly and the future holds promise for
mechanism-based novel diagnostics and therapeutics.
Keywords
angiogenic factors, placental growth factor, preeclampsia, pregnancy, proteinuria, soluble fms-like tyrosine
kinase 1, vascular endothelial growth factor

INTRODUCTION has been increasing [7]. Clinical manifestations may

Preeclampsia classically appears around 20 weeks of
gestation with symptoms of hypertension and pro-
teinuria. Profound peripheral vasoconstriction
along with decreased arterial compliance leading
to uncontrolled hypertension has been reported
[1,2]. The clinical diagnosis is usually based on a
blood pressure measurement greater than 140/
90 mmHg on two separate occasions, and urinary
protein excretion exceeding 300 mg/day. However,
in the absence of significant proteinuria, hyper-
tension in the presence of any end-organ damage,
such as impaired liver function, thrombocytopenia,
renal insufficiency, pulmonary edema, or cerebral
&&
disturbances, is sufficient to make a diagnosis [3 ].
Both mothers afflicted with preeclampsia and their
children may develop long-term complications [4].
Preeclampsia is seen globally in 3–5% of all preg-
nancies [5]. According to the World Health Organ-
ization, hypertension during pregnancy is a leading
cause of maternal mortality at 16% in industrialized
countries and up to 25% in developing countries [6].
In the United States, the incidence of preeclampsia
occur before or during pregnancy or even after child-
birth. Preeclampsia is one of the major causes for
preterm delivery, and if untreated, can result in fatal
complications to the mother and the fetus.
PATHOGENESIS OF PREECLAMPSIA
Preeclampsia is caused by placental dysfunction
(Stage 1) followed by the release of factors by
the diseased placenta into the maternal circula-
tion (Stage 2), inducing widespread endothelial
a
Massachusetts General Hospital and Harvard Medical School and
b
Beth Israel Deaconess Medical Center and Harvard Medical School,
Boston, Massachusetts, USA
Correspondence to S. Ananth Karumanchi, Beth Israel Deaconess
Medical Center 330 Brookline Avenue, RN 370D, Boston, MA
02215, USA. Tel: +1 617 667 1018; fax: +1 617 667 0445; e-mail:
sananth@bidmc.harvard.edu
Curr Opin Nephrol Hypertens 2015, 24:131–138
DOI:10.1097/MNH.0000000000000105

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Pathophysiology of hypertension

dysfunction that heralds the classic manifestations

KEY POINTS
 Preeclampsia is a placental disease, mediated by the
release of angiogenic factors into the maternal
circulation, inducing widespread endothelial
dysfunction, with hypertension and proteinuria,
classically presenting during the third trimester
of pregnancy.
 Soluble sFlt1, an antiangiogenic factor made in the
placenta, is upregulated in preeclampsia and
contributes to glomerular endothelial injury,
hypertension, and proteinuria. Increased sFlt1 levels
are associated with decreased circulating levels of free
VEGF and PlGF, resulting in systemic endothelial
dysfunction.
 Serum levels of both sFlt1 and PlGF may serve as both
diagnostic and prognostic markers in patients with
suspected preeclampsia.
 Targeting sFlt1 may safely ameliorate preeclampsia
and prolong pregnancy; however, randomized trials
are still needed.
 Preeclampsia is associated with hypertension, chronic
kidney disease, and cardiovascular disease in later life.
of the disease (Fig. 1) [8].
Placental disease
The placenta is integral to the development of pre-
eclampsia since in most cases removing the placenta
usually resolves the issue. During normal preg-
nancy, the trophoblasts, which are the cells that
constitute the outer layer of the blastocyst, permeate
the uterine spiral arteries. As part of this process,
trophoblasts adopt an endothelial phenotype,
expressing adhesion molecules classically found
on the surface of endothelial cells. The remodeled
vasculature allows for appropriate placental devel-
opment. In contrast, in the preeclamptic mother,
the vasculature remains unmodified, and, therefore,
the placental bed has blood flow that is aberrant and
incompatible with normal fetal development [9].
Recent studies using carefully phenotyped subjects
have shown that the defect in spiral artery remodel-
ing noted in preeclampsia occurs mostly in myome-
trial tissue and is not limited to preeclampsia alone
as it is also seen in human fetal growth restriction
[10]. The hypothesis that defective trophoblastic
invasion with associated uteroplacental hypoperfu-
sion may lead to preeclampsia is supported by

h Oxidative stress, Immunological/inflammatory

i Heme oxygenase NK cells, AT1-AA
Genetic factors
i COMT

Stage I Abnormal placentation

(0-16 weeks)
Small-for-
Reduced placental perfusion gestational age
infant

Stage II h Circulating sFlt-1, h sEng

(≥17 weeks) i Circulating PlGF and i VEGF, hAT1-AA
?Other maternal factors

Systemic vascular
dysfunction/capillary leak/vasospasm

Proteinuria Coagulation abnormalities (HELLP)

Hypertension Cerebral edema (eclampsia)
glomerular endotheliosis

FIGURE 1. Proposed schema for the evolution of preeclampsia. Multiple processes may be involved in the development of
preeclampsia, including elevated levels of circulating soluble form-like tyrosine kinase 1 (sFlt1), potentially superimposed on
poor maternal vascular health, and/or obesity. The development of systemic vascular dysfunction leads to clinical
manifestations. Reproduced with permission from Young et al. [8]. AT1, angiotensin II type I; COMET, catechol-O-
methyltransferase; HELLP, hemolysis, elevated liver enzymes, and low platelets syndrome; NK, natural killer.

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animal and human studies. Pathologic examination
of placentas from pregnancies with advanced pre-
eclampsia often reveals numerous placental infarcts
and sclerotic narrowing of arterioles. Typically, in
preeclamptic women, ultrasound estimation of ute-
roplacental blood flow is diminished and uterine
vascular resistance is increased. These vascular
changes related to mechanical constriction of the
uterine arteries or aorta in turn lead to placental
ischemia, hypertension, proteinuria, and, variably,
glomerular endotheliosis, in several animal species
[11,12]. However, placental ischemia alone, as seen
with intrauterine growth restriction (IUGR), does
not appear to be sufficient to produce preeclampsia.
Thus, although uteroplacental ischemia is an
important trigger of preeclampsia, it may be absent
in some cases and the maternal response to placen-
tal ischemia is variable. Hypoxia may contribute to
the abnormal placental development described
above; cytotrophoblasts cultured in vitro under
hypoxic conditions often fail to fully invade and
alter surface adhesion molecules [13]. However,
definitive evidence demonstrating placental
hypoxia as a causal factor has not been established.
Maternal endothelial dysfunction
During the first trimester of pregnancy, the
maternal systemic circulation undergoes significant
changes. Renal blood vessels increase in diameter,
and this vasodilatory response results in enhanced
renal plasma flow and glomerular filtration rate
(GFR). With the progression of preeclampsia, there
is profound systemic vasoconstriction with
decreases in GFR [14]. Generalized damage to the
endothelium of the maternal kidneys, liver, and
brain at the cellular level likely occurs following
the release of toxic factors from the diseased
placenta [15]. Many serum markers of endothelial
activation and endothelial dysfunction are deranged
in women with preeclampsia; these markers include
von Willebrand antigen, cellular fibronectin, soluble
tissue factor, soluble E-selectin, platelet-derived
growth factor, and endothelin. There is also exagger-
ated sensitivity to the vasopressors angiotensin II and
norepinephrine in women with preeclampsia [14].
Moreover, women who develop preeclampsia have
impaired endothelium-dependent vasorelaxation.
Compared to normotensive women, patients with
preeclampsia have problems with hypercoagulation.
In fact, activation of coagulation in preeclampsia
occurs early in the disease and often precedes clinical
symptomatology. Glomerular endotheliosis, a type
of renal thrombotic microangiopathy, is thought to
be responsible for the renal impairment present in
preeclampsia [16]. Preeclampsia is associated with
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Pathogenesis of preeclampsia Sircar et al.
increased fibrin deposition in the kidney glomerulus
[17]. Postmortem renal tissues from preeclamptic
patients have shown the presence of diffuse fibrin
deposition.
Soluble fms-like tyrosine kinase 1 as a
mediator of the maternal syndrome
Although the cause of preeclampsia is still unclear,
its manifestations, including endothelial dysfunc-
tion, hypertension, and proteinuria, are thought to
be mediated by high circulating concentrations of
antiangiogenic proteins such as soluble fms-like
tyrosine kinase 1 (sFlt1 or sVEGFR1) [18,19]. sFlt1
induces endothelial dysfunction by inhibiting
vascular endothelial growth factor (VEGF) signal-
ling, particularly in endothelial cells that are fenes-
trated and have constitutive expression of VEGF,
such as those that reside in the glomerulus of the
kidney [20]. Several isoforms of sFlt1 have been
reported; however, the isoform sFlt1-14 appears to
be the predominant protein that circulates in
patients with preeclampsia [21].
In preeclampsia, sFlt1 expression is upregulated,
causing systemic levels of sFlt1 to rise during preg-
nancy, which subsequently fall postpartum [19].
The increased circulating sFlt1 levels in patients
with preeclampsia are associated with decreased
circulating levels of free VEGF and placental growth
factor (PlGF), resulting in endothelial dysfunction
(Fig. 2) [14]. These deficiencies can be rescued by
administration of exogenous VEGF and PlGF. In
addition, VEGF and PlGF cause microvascular
relaxation of rat renal arterioles in vitro, which are
blocked by sFlt1. Administration of sFlt1 to preg-
nant rats induces hypertension, proteinuria, and
glomerular endotheliosis, the classic lesion of
preeclampsia [19]. These observations suggest that
excess circulating sFlt1 contributes to the pathogen-
esis of preeclampsia. Reduced maternal eNOS/nitric
oxide exacerbates the sFlt1-related preeclampsia-
like phenotype through activation of the endo-
thelin system [22].
Many molecular mechanisms are thought to
contribute to renal dysfunction, including glomer-
ular capillary endotheliosis, dysregulation of the
glomerular filtration apparatus, and podocyte loss.
The renal complications of preeclampsia are similar
to the toxicities related to antiangiogenesis therapy
&&
given to cancer patients [23,24,25 ]. Under normal
physiologic conditions, VEGF appears to play a
major role in maintaining glomerular integrity. This
role was clarified in a study involving adrenal
cortical endothelial cells in which the presence of
VEGF was found to induce endothelial fenestra-
tions. When intraglomerular VEGF levels decrease,
www.co-nephrolhypertens.com 133
Pathophysiology of hypertension

Anticoagulant and
VEGF vasodilatory factors

PIGF

FLT-I Healthy endothelial cell

Healthy Blood vessel
placenta
sFLT-I

Procoagulant and
vasoconstricting factors

Dysfunctional endothelial cell

Blood vessel

Preeclampsia
placenta

FIGURE 2. Role of sFlt1 and other antiangiogenic markers in maternal endothelial dysfunction of preeclampsia. In
preeclampsia, excess placental sFlt1 traps circulating and tissue VEGF and PlGF, and prevents their interaction with
endothelial cell-surface receptors, leading to endothelial dysfunction. Reproduced with permission from Karumanchi et al. [14].
PLGF, placental growth factor; VEGF, vascular endothelial growth factor.

capillary endothelial cells typically swell and capil-
lary loops collapse, resulting in a drop in GFR and
rise in urinary protein excretion [26,27]. Further-
more, VEGF has been shown to be crucial in the
maintenance of not only the renal vascular bed, but
also the hepatic vascular bed. VEGF also dynami-
cally regulates fenestrations in the sinusoidal endo-
thelial cells during liver organogenesis.
Although its binding sites lie on glomerular
endothelial cells, VEGF is strongly expressed by
podocytes. An evolving area of interest is the shed-
ding of podocytes following functional blockade of
VEGF. This process coincides with advanced disease,
often deemed irreversible, and therefore, detection
does not lend itself to intervention. However, the
use of urinary podocyte excretion as a biomarker for
preeclampsia has been explored [28].
Other factors released by the placenta act syn-
ergistically with sFlt1 to induce an antiangiogenic
environment. Soluble endoglin (sEng), an antian-
giogenic factor that acts by inhibiting TGF-b signal-
ing in the vasculature, has been confirmed in
rodents to act in concert with sFlt1 to induce severe
preeclampsia involving fetal growth restriction,
thrombocytopenia, and cerebral edema [29,30].
sEng is increased in the sera of preeclamptic women
2–3 months before clinical signs of preeclampsia
develop and its blood levels correlate with disease
severity [31–33].
Upstream regulators of soluble fms-like
tyrosine kinase 1 production
The upstream regulation of sFlt1 has been a topic of
great interest. Numerous pathways have been impli-
cated such as deficient heme oxygenase expression,
placental hypoxia, genetic factors, oxidative stress,
inflammation, altered natural killer (NK) cell signal-
ing, and, more recently, deficient catechol-O-
methyl transferase [34]. However, it is not known
if any of these pathways are relevant in human
disease. Of particular interest has been the role of
the complement pathway, angiotensin II, and
endometrial VEGF.
Alterations in several components of the alter-
nate complement pathway have recently been
reported in preeclampsia [35,36]. The role of the
complement system in mediating human renal dis-
ease has long been recognized in immune-complex
excess syndromes, including systemic lupus eryth-
ematosus, and dense deposit disease in which no
immunoglobulin (Ig) is present. Over the past
15 years, mutations in complement regulatory
genes have been found to predispose an individual
to thrombotic microangiopathies such as atypical
hemolytic uremic syndrome, C3 and C1q glomer-
ulopathies, and preeclampsia [37]. Targeted inhi-
bition of the complement pathway has been
shown to relieve preeclampsia in mouse models
[38]. As further investigation is performed into the

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genetic underpinnings of this disease, it is possible
that complement dysregulation plays a role
upstream of sFlt1 in a subset of preeclampsia cases.
Women with preeclampsia have a heightened
sensitivity to the hypertensive effects of angiotensin
II. Studies have revealed that angiotensin II type I
(AT1) agonistic autoantibodies may contribute to
this process [39]. AT1 antibodies have been demon-
strated to induce placental sFlt1 production and
cause preeclampsia in pregnant mice [40]. However,
it is unknown whether in humans, AT1 alterations
in plasma modulate angiogenic factors.
Very recently, endometrial upregulation of
VEGF has been shown to lead to preeclampsia in
mice by upregulating placental sFlt1 production
&&
[41 ]. However, the majority of the sFlt1 is free or
uncomplexed in circulation in patients with pre-
eclampsia [42]. More data are needed to evaluate
the role of endometrial VEGF as an early event in
the pathogenesis of preeclampsia.
Although the placenta is the major source of
sFlt1 production, recent data suggest that syncytial
knots in the placenta may detach, and free, trans-
criptionally active syncytial aggregates, that
represent an autonomous source of sFlt1 delivery
into the maternal circulation, may also contribute
to the high circulating levels seen in preeclampsia
[43,44]. More work on the basic biology of syncyti-
alization may shed clues on the underlying mole-
cular defect in preeclampsia.
BIOMARKER STUDIES IN PREECLAMPSIA
Evidence from a number of laboratories suggests
that the maternal syndrome of preeclampsia is an
antiangiogenic state due to impaired VEGF signaling
in the renal glomerulus and other microvascular
beds. As a surrogate of VEGF impairment, PlGF levels
in the plasma have emerged as an attractive bio-
marker. PlGF, a VEGF family member, is a proangio-
genic protein abundant during pregnancy, which
binds to the Flt1 receptor, but not other VEGF
receptors such as kinase insert domain receptor
(KDR). As sFlt1 levels rise, free PlGF levels drop,
and the sFlt1/PlGF ratio correlates with preeclamp-
sia phenotypes [32,45]. Working with industry
partners, our group, along with other colleagues,
has developed highly sensitive, specific, and robust
high-throughput assays to quantitate levels of sFlt1
and free PlGF in plasma and serum [42,46–48].
Several groups have established that sFlt1 and
PlGF levels can be used to differentiate preeclampsia
from diseases that mimic preeclampsia such as
chronic hypertension, gestational hypertension,
kidney disease, and gestational thrombocytopenia
&&
[49,50 ,51,8]. We also demonstrated that the
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Pathogenesis of preeclampsia Sircar et al.
plasma sFlt1/PlGF ratio in the triage setting predicts
adverse maternal and perinatal outcomes (occurring
within 2 weeks) in women with suspected preterm
preeclampsia. This ratio alone outperformed stand-
ard clinical diagnostic measures including blood
pressure, proteinuria, and uric acid. Importantly,
angiogenic factor levels in the triage setting corre-
lated with preterm delivery, an observation that has
&&
now been confirmed by several groups [52–54,55 ].
Furthermore, we also demonstrated that women
diagnosed with preeclampsia, but with a normal
angiogenic profile, are not at risk for adverse
maternal or fetal outcomes [56].
NOVEL THERAPEUTICS
Based on the recent advances presented above, a
number of different strategies are being explored
to allow carrying of the fetus to full term. These
strategies target angiogenic factors using both
in-vitro and in-vivo models to restore angiogenic
balance. These include generation of recombinant
proteins similar in function to VEGF, selective
depletion of sFlt1 with antibodies or an extra-
corporeal device, as well as isolation of small mole-
cules, such as siRNA or small-molecule inhibitors of
sFlt1 production.
In recent years, a number of successful in-vitro
studies have bolstered confidence in these targeted
therapies. Li et al. demonstrated that administration
of VEGF-121 to a rodent model of preeclampsia
improved hypertension, proteinuria, glomerular
endotheliosis and reverted sFlt1-induced changes
in gene expression [20]. In 2010, Gilbert et al. [57]
showed that infusion of VEGF-121 lowered blood
pressure and preserved renal function in rats with
placental ischemia-induced hypertension. In the
same year, Bergmann et al. [58] showed that coad-
ministration of adenovirus-expressing VEGF in a
rodent model of preeclampsia resulted in marked
reduction of free sFlt1, allowing for renal recovery
and normalized blood pressure. Interestingly, pra-
vastatin was administered to mice overexpressing
placental specific sFlt1. The study showed increased
PlGF expression and decreased sFlt1 levels in the
circulation, allowing relief of preeclamptic symp-
toms [59]. A clinical trial to test the safety of statins
in women with established preeclampsia has been
initiated in the United Kingdom [60]. Recombinant
PlGF has also shown to mitigate the signs and
symptoms of preeclampsia in a mouse model of
preeclampsia [61]. More recently, hydrogen sulfide
has been shown to promote VEGF signaling and has
emerged as an attractive therapeutic molecule to
counteract the toxic effects of sFlt1 in the vascula-
&&
ture [62 ].
www.co-nephrolhypertens.com 135
Pathophysiology of hypertension
Several human case reports support the idea that
sFlt1 may be a viable therapeutic target in humans
with preeclampsia. Reduction of sFlt1 levels resulted
in the resolution of signs of preeclampsia in cases of
parvovirus-induced hydrops [63], mirror syndrome
[64], and fetal demise in twin pregnancies [65]. It
was reassuring to observe that the reduction of sFlt1
levels was well tolerated in pregnancy without any
adverse effects.
Recently, our group selectively removed posi-
tively charged sFlt1 molecules using a negatively
charged dextran sulfate cellulose column [66]. In
a pilot study in eight pregnant women with preterm
preeclampsia, dextran sulfate apheresis led to the
reduction in sFlt1 levels and improved proteinuria
and hypertension, without any apparent adverse
effects to either the mother or the fetus. Extra-
corporeal removal of sFlt1 was performed up to four
times in a single patient. She remained pregnant for
23 days. Two patients were treated twice; one
remained pregnant for 15 days and the other for
19 days. In the untreated cohort, the average pro-
longation of pregnancy was 3.6 days [66]. This
study demonstrates that selective removal of sFlt1
is a well-tolerated method of prolonging gestation
in severe preterm preeclamptic patients. Further
modifications in column design may allow for
increased sFlt1 clearance, and further benefit both
the fetus and the mother.
Experimental studies suggest that the hormone
relaxin, a naturally occurring ovarian hormone,
may be used to ameliorate preeclampsia by improv-
ing vascular compliance and upregulating locally
produced VEGF [67]. A phase I study to test the
safety of human relaxin in women with preeclamp-
sia is now underway [68].
PREECLAMPSIA AND CHRONIC KIDNEY
DISEASE
In women with preexisting kidney disease, preg-
nancy-related adverse outcomes depend on the
degree of renal impairment, the amount of protei-
nuria, and the severity of hypertension [7]. Several
glomerular diseases may occur in women of child-
bearing age. Pregnancy in those renal patients is
generally associated with less maternal and fetal
complications if their renal disease has been in
remission for a minimum of 6 months [36]. Prema-
turity, IUGR, and preeclampsia are also increased in
renal transplant patients [35]. Recent data examin-
ing pregnancy outcomes after kidney donation in
young women of childbearing age suggest that these
women have a higher risk of gestational hyperten-
sion and preeclampsia during pregnancy [69]. How-
ever, there were no significant differences between
136 www.co-nephrolhypertens.com
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
donors and nondonors with respect to rates of pre-
term birth (8% and 7%, respectively) or low birth
weight (6% and 4%, respectively).
The most significant maternal complication
with preeclampsia is the development of end-stage
renal disease (ESRD). In 2008, the development of
ESRD in patients with prior episodes of preeclampsia
was examined [70]. Among women who had been
pregnant two or more times, preeclampsia during
the first pregnancy was associated with a relative risk
of ESRD of 3.2, preeclampsia during the second
pregnancy increased the relative risk to 6.7, and
preeclampsia during both pregnancies was associ-
ated with the relative risk of 6.4 [70]. Among women
who had been pregnant three or more times, pre-
eclampsia during first pregnancy was associated
with a relative risk of ESRD of 6.3, and preeclampsia
during second and third pregnancies was associated
with a relative risk of 15.5. Having a low-birth-
weight or preterm infant increased the relative risk
of ESRD. The results were similar after adjustment
for possible confounders and after exclusion of
women who had kidney disease, rheumatic disease,
essential hypertension, or diabetes mellitus before
pregnancy. A follow-up study from the same inves-
tigators suggested that preeclampsia per se, and not
familial factors, contributed to chronic kidney dis-
ease [71].
The prevalence of hypertension in women with
previous preeclampsia is three to four times the
risk found in women without preeclampsia [72].
Similarly, the risk of death from cardiovascular dis-
ease and cerebrovascular disease is about two-fold
greater in women with a history of preeclampsia
[73–75].
CONCLUSION
Preeclampsia is a gestational disease characterized
by glomerular endotheliosis and is associated with
hypertension and proteinuria (see Fig. 1). As the
role of sFlt1 and PlGF becomes clearer, a new mode
of noninvasive diagnosis may be possible. In
addition, novel therapies are evolving to selectively
remove sFlt1 or antagonize sFlt1 in order to stall
disease progression. There is great hope that in the
future all preeclamptic pregnancies will be taken to
full term, without any long-term maternal compli-
cations. Preeclampsia also contributes significantly
to chronic kidney disease and cardiovascular disease;
further exploration of the mechanism has the poten-
tial to advance cardiovascular screening and preven-
tion in this large group of very high-risk women.
Acknowledgements
None.
Volume 24  Number 2  March 2015

Financial support and sponsorship
M.S. is supported by NIH T32 award, R.T. by NIH K24
award, and S.A.K. is an investigator of the Howard
Hughes Medical Institute.
Conflicts of interest
S.A.K and R.T. have financial interests in Aggamin
Therapeutics. R.T. is a consultant for Roche Diagnostics.
S.A.K. is a consultant for Siemens, and has grant funding
from Thermofisher. S.A.K. and R.T. are coinventors on
patents related to angiogenic biomarkers in preeclampsia
that are held by Harvard hospitals.
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Volume 24  Number 2  March 2015