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Clinical and biochemical evidence of endothelial cell dysfunction in the pregnancy syndrome preeclampsia
J M Roberts1, R N Taylor, A Goldfien
1Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco 94143.
Insights
Preeclampsia, a major pregnancy disorder, stems from placental issues, not just high blood pressure. Reduced placental perfusion leads to endothelial cell dysfunction, causing widespread organ damage and characteristic preeclampsia symptoms.
Area of Science:
- Obstetrics and Gynecology
- Maternal-Fetal Medicine
- Pathophysiology
Background:
- Preeclampsia remains a leading cause of maternal and infant mortality despite extensive research.
- Current therapy is limited to empiric early delivery due to incomplete understanding of the syndrome.
- Focus on hypertension overshadows other critical pathophysiological changes.
Purpose of the Study:
- To propose a unifying hypothesis for preeclampsia pathophysiology.
- To highlight the role of placental dysfunction and endothelial cell injury.
- To differentiate preeclampsia from mere pregnancy-induced hypertension.
Main Methods:
- Review of existing literature and clinical observations.
- Analysis of pathophysiological markers including endothelial morphology and circulating factors.
- In vitro studies assessing endothelial cell activation by blood factors.
Main Results:
- Reduced placental perfusion, secondary to implantation defects, is the likely earliest pathophysiological event.
- Placental factors injure or activate endothelial cells, leading to dysfunction.
- Evidence includes abnormal endothelial morphology, increased fibronectin, and mitogenic activity in affected women.
Conclusions:
- Preeclampsia pathophysiology involves widespread endothelial cell dysfunction, not solely hypertension.
- The syndrome originates from placental issues leading to systemic effects.
- Preeclampsia is a complex disorder with multi-organ involvement beyond elevated blood pressure.
Abstract:
The pregnancy disorder preeclampsia continues as a major cause of maternal and infant mortality and morbidity. Despite intensive research since its recognition 100 years ago, our lack of understanding is evidenced by therapy which remains empiric, early delivery. Part of our failure to more completely understand the syndrome is due to excessive attention to the blood pressure elevation which accompanies the disorder, to the exclusion of a panoply of other physiologic aberrations. Although hypertension, if markedly elevated, can lead to maternal morbidity, it is not usually an important contributor to the pathophysiology of preeclampsia. It is primarily important as a marker for vasoconstriction, which in association with activation of coagulation reduces perfusion to many organs, including the fetal-placental unit. The earliest and likely most important pathophysiologic change is reduced placental perfusion secondary to abnormal implantation and/or a relative increase in placental mass. We propose that reduced placental perfusion results in the production of agent(s) by this organ, which injures or activates endothelial cells. The resulting endothelial cell dysfunction increases sensitivity to normal endogenous pressors, activates the coagulation cascade, and increases vascular permeability. These changes produce the characteristic pathophysiologic changes of the disorder. Evidence supporting this hypothesis includes abnormal endothelial morphology long recognized in glomerular capillaries, increased circulating fibronectin, and increased plasma mitogenic activity that long antedates the clinical disorder. In addition, an agent(s) is present in the blood of these women which activates endothelial cells in vitro as evidenced by increased release of [51Cr] chromium and increased production of PDGF. Preeclampsia is clearly more than "pregnancy induced hypertension."