CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 5, June 2013
174
AFRICA
Maternal imbalance between pro-angiogenic and
anti-angiogenic factors in HIV-infected women with
pre-eclampsia
NALINI GOVENDER, THAJASVARIE NAICKER, JAGIDESA MOODLEY
Abstract
Angiogenic imbalance contributes to the development of pre-
eclampsia. We evaluated the protein expression of the pro-
angiogenic placental growth factor (PlGF) and transforming
growth factor beta 1 (TGF-
β
1
) compared with the anti-angio-
genic soluble fms-like tyrosine kinase receptor (sFlt1) and
soluble endoglin (sEng) in HIV-infected normotensive and
pre-eclamptic pregnancies.
Blood was obtained from 110 pregnant women, enrolled
in four groups, namely, HIV-negative normotensives (27);
HIV-positive normotensives (31); HIV-negative pre-eclamp-
tics (27) and HIV-positive pre-eclamptics (25), and was used
to measure PlGF, TGF-
β
1
, sFlt1 and sEng levels.
Increased sFlt1 and sEng levels were associated with the
pre-eclamptics (HIV negative and positive) compared with
their counterparts. Decreased PlGF levels were observed
between the HIV-negative pre-eclamptics versus HIV-nega-
tive normotensives, but levels differed significantly (
p
=
0.02) among the normotensives (HIV negative and positive).
TGF-
β
1
remained unchanged across all groups. Higher
sEng/TGF-
β
1
ratios were associated with the pre-eclamptics
(HIV negative and positive) compared with their counter-
parts. This study demonstrated increased sFlt1 and sEng
levels in pre-eclamptic compared with normotensive preg-
nancies, irrespective of the HIV status.
Keywords:
sFlt1, pre-eclampsia, anti-angiogenic factors, HIV
Submitted 27/7/11, accepted 18/4/13
Cardiovasc J Afr
2013;
24
: 174–179
DOI: 10.5830/CVJA-2013-029
Pre-eclampsia, a clinical syndrome unique to human pregnancy
is characterised by new-onset hypertension and proteinuria,
which present after the 20th week of gestation.
1-4
Although
several studies in the last few decades have investigated the
pathogenesis of this disorder, limited progress has been made in
establishing the exact cause.
5,6
Currently, pre-eclampsia is reported to be a two-stage disorder,
namely, a pre-clinical/asymptomatic, and a clinical stage.
2,7
The
first stage is characterised by abnormal placentation leading to
a hypoxic placenta, oxidative stress and immune dysregulation,
while the second stage is characterised by the placental discharge
of soluble factors, such as sFlt1 and sEng into the maternal
circulation, resulting in widespread endothelial dysfunction and
the clinical syndrome of hypertension, proteinuria, intrauterine
growth restriction (IUGR) and thrombocytopenia.
2,7-10
Both pre-eclampsia and HIV infection are common conditions
in sub-Saharan Africa and major causes of maternal deaths.
11
Recent studies have reported that the persistent infection of
HIV-infected individuals contributes to the development of
chronic arterial injury and subsequent endothelial damage,
atherosclerosis and thrombosis.
12
Furthermore, untreated
HIV-infected patients may be prone to endothelial dysfunction.
12
HIV infection also seems to affect the mechanisms implicated in
the aetiology of pre-eclampsia and IUGR.
Normal pregnancy is characterised by an altered immune
sensitivity, thereby allowing maternal resistance against any
infection and foetal tolerance, while pre-eclampsia is a hyper-
active immune response.
13,14
It is plausible that the immune
insufficiency stimulated by HIV together with the normal
immune changes of pregnancy may reduce a predisposition to the
immune hyper-reactivity that is associated with pre-eclampsia.
15-17
Therefore it is not surprising that some reports have shown
that a reduced rate of pre-eclampsia prevails among untreated
HIV-infected patients in comparison with those on highly active
antiretroviral therapy (HAART).
14,18
The administration of HAART is reported to enhance
maternal immune reconstitution by re-establishing the mother’s
immune response to foetal antigens, and consequently making
the woman susceptible to the development of pre-eclampsia.
14
Conflicting reports however, have created uncertainty as to
whether HIV-infected pregnant women on HAART have lower
rates of pre-eclampsia.
17-19
This uncertainty may impact on both
maternal and perinatal morbidity and mortality in a geographical
region with a high prevalence of HIV.
Angiogenic biomarkers have been suggested for the early
detection of pre-eclampsia in high-income countries, despite the
lack of robust evidence for their use.
4,17
Therefore, this study set
out to examine the role of pro- and anti-angiogenic factors in
the aetiology of pre-eclampsia in a setting of high rates of HIV
infection.
Methods
Institutional ethical and regulatory approvals were obtained.
Clinical characteristics such as maternal and gestational age,
parity, maternal, baby and placental weight, and blood pressure
were collected during antenatal recruitment.
Venous blood samples were collected from 110 pregnant
black African women at term attending a tertiary maternity unit
in Durban, KwaZulu-Natal, South Africa. All blood samples
Optics and Imaging Centre, University of KwaZulu-Natal,
South Africa
NALINI GOVENDER, PhD,
THAJASVARIE NAICKER, PhD
Women’s Health and HIV Research Group, University of
KwaZulu-Natal, South Africa
JAGIDESA MOODLEY, MB ChB, FCOG, FRCOG (UK), MD
