Endothelial and placental mechanisms in pre-eclampsia
THE CONTEXT
Vascular mediators, inflammation and placental hypoxia contribute to hypertension and endothelial dysfunction.
Vascular mediators
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Nitric oxide relaxes vascular smooth muscle, inhibits platelet aggregation and prevents intervillous thrombosis. Its deficiency contributes to hypertension.
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Endothelin-1 is synthesized by endothelial cells. It is a potent vasoconstrictor and contributes to hypertension.
Inflammation and oxidative injury
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Cytokines derived from activated leukocytes, including tumor necrosis factor and interleukin-6, cause endothelial injury.
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Abnormal lipid metabolism increases oxidative stress. Lipid peroxides, reactive oxygen species and superoxide anion radicals cause endothelial injury and dysfunction.
Placental hypoxia and angiogenesis
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Poor cytotrophoblastic invasion of the spiral arteries causes chronic placental hypoxia.
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Chronic hypoxia activates endoplasmic reticulum apoptotic pathways, increases oxidative stress and promotes release of angiotensin-II, endoglin, Flt-1 and uric acid. The increased systemic inflammatory response causes endothelial damage.
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Placental growth factor is an angiogenic protein secreted by placental syncytiotrophoblast and promotes placental angiogenesis. Soluble fms-like tyrosine kinase-1 is described as a circulating antiangiogenic factor.