Endothelial dysfunction in preeclampsia

Several years ago the hypothesis was advanced that alterations of endotheli al function could explain much of the pathophysiology of preeclampsia. Sinc e that time, extensive data have been generated to support the hypothesis. Markers of endothelial activation can be demonstrated in women with overt p reeclampsia. More importantly, many of these markers precede clinically evi dent disease and disappear with resolution of the disease. The original pos tulate was that materials produced by the poorly perfused placenta, which i s characteristic of preeclampsia, entered the systemic circulation and alte red endothelial cell activity. This was proposed to change vascular sensiti vity to circulating pressors, activate coagulation, and reduce vascular int egrity resulting in the pathophysiological changes of preeclampsia. As data have accumulated it hits become increasingly evident that the insul t 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 responsib le agent(s) will not be unique molecules but rather usual molecules present in excessive amounts. The hypothesis has been expanded to invoke involveme nt of the maternal constitution in the generation of endothelial injury and injurants. This concept is stimulated by the observation that reduced plac ental perfusion per se is not sufficient to generate the maternal syndrome. Women with growth-restricted fetuses frequently are not preeclamptic. Plac ental bed biopsies from not only growth-restricted but also prematurely bor n infants demonstrate failure of the physiological remodeling of decidual v essels responsible for the reduced placental perfusion of preeclampsia. Thi s has led to the concept that preeclampsia is secondary to an interaction o f reduced placental perfusion and maternal factors. Interestingly these mat ernal factors, obesity, insulin resistance, black race, hypertension, and e levated plasma homocysteine concentration are all risk factors for atherosc lerosis in later life.