Circulating Endothelial Progenitor Cells and Preeclampsia in Women with Placental Malaria
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Date
2019-03
Authors
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Publisher
University Of Ghana
Abstract
Background
Placental malaria and preeclampsia are major complications of pregnancy associated with high
incidence of maternal/foetal Morbidity and mortality particularly in sub-Saharan Africa.
Similarities in pathophysiology such as systemic inflammation and generalized endothelial
activation/dysfunction exist and are exacerbated in concurrent situations. The combined
pathologic and immunologic effects of these pregnancy disorders, prevalent in malaria endemic
regions, have not been tested. This study evaluated the pathologic risk associated with
Plasmodium falciparum infection in the placenta and the outcome of preeclampsia. Immune
mediators associated with placental malaria and the risk of preeclampsia were evaluated. In
addition, the relationship between endothelial cell phenotypes implicated in vascular
activation/injury/damage/repair and the factors that mediate their release were assessed.
Methods
A total of 140 pregnant women (18 - 42 years) diagnosed with and without preeclampsia were
recruited into the study in Accra, Ghana. Peripheral blood samples were collected at delivery while
cord blood, placental intervillous blood and placental biopsies were collected after delivery.
Circulating endothelial cells (cECs) and circulating endothelial progenitor cell phenotypes (cEPCs,
mEPCs and iEPCs) were quantified by flow cytometry. Immunological (inflammatory and
angiogenic) factors were tested by multiplex ELISA using plasma separated from whole blood.
Placental biopsies were histologically evaluated for unique placental lesions and placental malaria
(classified as active and past infections).
Results
Of 133 placentas scored for placental malaria, women diagnosed with preeclampsia had 39
(29.3%) and 15 (11.3%) active and past infections respectively while the non-preeclamptic women had 25 (18.8%) active infections and 6 (4.5%) past infections. Both active (adjusted
odds ratio (AOR) 6.7, 95% CI 2.3 – 18.9; P < 0.0001) and past infections (AOR 11.6, 95% CI
3.0 – 45.8; P < 0.0001) increased the risk of preeclampsia. This association was enhanced in
primigravidae (AOR 6.6, 95% CI 2.4 – 18.2; P < 0.0001) and in women with pathological
alterations in the placenta (AOR 3.0, 95% CI 1.2 – 7.5; P < 0.019). The preeclamptic
pregnancies with active placental parasites showed higher levels of proinflammatory and antiangiogenic
markers. In multivariate analysis, active parasite infection (AOR = 7.14, 95% CI =
1.1 – 44.7; P = 0.04), past infection (AOR = 12.9, 95% CI = 1.1 – 155.5; P = 0.04),
primigravidity (AOR = 7.2, 95% CI = 1.1 – 48.0; P = 0.04) and increased levels of the
plasminogen activator inhibitor (PAI)-1 molecule (AOR = 7.1, 95% CI = 1.3 – 38.3; P = 0.02)
were all associated with placental malaria.
Furthermore, proportions of endothelial cell phenotypes were higher in the placenta and cord
compared to peripheral blood. Alterations in their levels correlated strongly with angiogenic
factors that stimulate their release mostly in non-preeclamptic compared to preeclamptic
pregnancies.
Conclusion
Findings from this study have demonstrated that the pathophysiology of preeclampsia is
pathologically and immunologically exacerbated in women exposed to placental malaria. In
addition, endothelial cell phenotypes that contribute to vascular homeostasis and the factors
that mediate their release into circulation are altered. Altogether, this study provides a new
paradigm in assessing preeclampsia in malaria endemic regions.
Description
PhD.Molecular Cell Biology of Infectious Diseases
Keywords
Placental Malaria, Foetal Morbidity, Plasmodium Falciparum, Sub-Saharan Africa