Preeclampsia is a low-grade systemic inflammatory condition in which oxidative stress and endothelial dysfunction occurs. Plasma levels of soluble receptor for
vascular endothelial growth factor (VEGFR)-1, also known as sFlt1 (soluble
fms-like tyrosine kinase 1), an antiangiogenic factor have been reported to be elevated in
preeclampsia. It was reported that pregnant mice deficient in
catechol-O-methyltransferase (COMT) activity show a
preeclampsia-like phenotype due to a deficiency or absence of
2-methoxyoestradiol (2-ME), a natural metabolite of
estradiol that is elevated during the third trimester of normal human pregnancy. Additionally,
autoantibodies (AT1-AAs) that bind and activate the
angiotensin II receptor type 1 a (AT1 receptor) also have a role in
preeclampsia. None of these abnormalities are consistently seen in all the patients with
preeclampsia and some of them are not specific to pregnancy.
Preeclampsia could occur due to an imbalance between pro- and antiangiogenic factors.
VEGF, an
angiogenic factor, is necessary for the transport of
polyunsaturated fatty acids (PUFAs) to endothelial cells. Hence reduced
VEGF levels decrease the availability of PUFAs to endothelial cells. This leads to a decrease in the formation of anti-inflammatory and angiogenic factors:
lipoxins, resolvins, protectins, and maresins from PUFAs.
Lipoxins, resolvins, protectins, maresins, and PUFAs suppress
insulin resistance; activation of leukocytes, platelets, and macrophages; production of
interleukin-6 and
tumor necrosis factor-α; and oxidative stress and endothelial dysfunction; and enhance production of
prostacyclin and
nitric oxide (NO).
Estrogen enhances the formation of
lipoxin A4 and NO. PUFAs also augment the production of NO and inhibit the activity of
angiotensin-converting enzyme and antagonize the actions of
angiotensin II. Thus, PUFAs can prevent activation of
angiotensin II receptor type 1 a (AT1 receptor). Patients with
preeclampsia have decreased plasma
phospholipid concentrations of
arachidonic acid (AA),
eicosapentaenoic acid (EPA), and
docosahexaenoic acid (DHA), the precursors of
lipoxins (from AA), resolvins (from EPA and DHA), and protectins (from DHA) and
prostaglandin E1 (
PGE1 from DGLA: dihomo-γ-
linolenic acid) and
prostacyclin (PGI2 derived from AA). Based on these evidences, it is proposed that
preeclampsia may occur due to deficiency of PUFAs and their anti-inflammatory products:
lipoxins, resolvins, protectins, and maresins.