Abstract
Several years ago the hypothesis was advanced that alterations of endothelial function
could explain much of the pathophysiology of preeclampsia. Since that time, extensive
data have been generated to support the hypothesis. Markers of endothelial activation
can be demonstrated in women with overt preeclampsia. More importantly, many of these
markers precede clinically evident disease and disappear with resolution of the disease.
The original postulate was that materials produced by the poorly perfused placenta,
which is characteristic of preeclampsia, entered the systemic circulation and altered
endothelial cell activity. This was proposed to change vascular sensitivity to circulating
pressors, activate coagulation, and reduce vascular integrity resulting in the pathophysiological
changes of preeclampsia.
As data have accumulated it has become increasingly evident that the insult to the
endothelium is neither toxicity nor nonspecific injury but rather can better be characterized
as endothelial activation. Candidate molecules have been suggested but not established.
It seems likely that the responsible agent(s) will not be unique molecules but rather
usual present in excessive amounts. The hypothesis has been expanded to invoke involvement
of the maternal constitution in the generation of endothelial injury and injurants.
This concept is stimulated by the observation that reduced placental perfusion per
se is not sufficient to generate the maternal syndrome. Women with growth-restricted
fetuses frequently are not preeclamptic. Placental bed biopsies from not only growth-restricted
but also prematurely born infants demonstrate failure of the physiological remodeling
of decidual vessels responsible for the reduced placental perfusion of preeclampsia.
This has led to the concept that preeclampsia is secondary to an interaction of reduced
placental perfusion and maternal factors. Interestingly these maternal factors, obesity,
insulin resistance, black race, hypertension, and elevated plasma homocysteine concentration
are all risk factors for atherosclerosis in later life.
Keywords:
Endothelium - preeclampsia - oxidative stress - cytokine - atherosclerosis
