Sera From Preeclamptic Women Specifically Activate Human Umbilical Vein Endothelial Cells In Vitro: Morphological and Biochemical Evidence

Abstract

Endothelial cell dysfunction could explain many of the pathophysiological changes observed in preeclampsia. Markers of endothelial cell activation including increased circulating Von Willebrand factor (VWF) and cellular fibronectin (cFN) antedate clinically evident disease. We have therefore proposed that alteration of endothelial cell function by circulating agent(s) produced by the placenta initiates the clinical syndrome. This hypothesis predicts that there are a factor(s) in the blood of women with preeclampsia that are capable of altering endothelial cell function. We and others have examined in vitro interactions of maternal serum and endothelial cells to test this hypothesis. Our initial report indicating increased release of [51Cr]chromate from human umbilical vein endothelial cells (HUVE) suggested a lethal, lytic effect of serum from preeclamptic women. However, more specific indicators of endothelial cell structure and function do not support such a nonspecific effect. The morphology of HUVE was minimally altered after exposure to sera of preeclamptic women, and the entry of propidium iodide entry into cells, a sensitive indicator of membrane integrity, also was not increased. These findings, in combination with the increased expression of mRNA for platelet-derived growth factor (PDGF), suggest endothelial cell activation rather than cell death in response to sera from preeclamptic women. Comparison of the effects of endotoxin and sera from preeclamptic women also supports the specificity of this response. Whereas endotoxin strikingly increased VWF on the surface of HUVE and tissue factor activity in conditioned media while minimally increasing cFN, preeclamptic sera increased cFN but had no demonstrable effect on VWF or tissue factor activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Excessive stimulation of poly(ADP‐ribosyl)ation contributes to endothelial dysfunction in pre‐eclampsia

“…Although an early study highlighted a cytotoxic effect of serum from preeclamptic donors, more recent evidence supports an outcome of endothelial activation as opposed to premature decline (Roberts et al, 1992). Our own data suggest that the active plasma factor in pre-eclampsia does not induce apoptosis or necrosis within endothelial cells, at least under the culture period specified, but instead attenuates endothelial-dependent vasoreactivity, through a PARP-dependent pathway.…”

Retraction: Etiopathology of preeclampsia — Recent progress from the perspective of a poor/ischemic placenta

“…32,33) Serum from preeclamptic women causes endothelial activation in human umbilical vein endothelial cells in vitro. 34) Impaired endothelial function can be demonstrated by brachial artery flow-mediated dilation three years after a preeclamptic pregnancy. 35) It is unknown whether this is a cause or effect of the preeclamptic pregnancy.…”

Hypertension in pregnancy

“…Also, in most settings cells appear normal and maintain structural integrity. 76 Thus, the nature of the dysfunction would suggest that the responsible factor is not a toxin but more likely a usual factor present inappropriately or at higher than usual concentration.…”

“…Increased Cr51 release 238 Increased lipid uptake 239 Increased expression of PDGF ␤-chain mRNA 240 Increased prostacyclin release 241 Increased cFN release 76 Increased nitric oxide (NO) release 242 Increased nitric oxide synthase (NOS) expression 243 Reduced endothelial cell proliferation 244 Increased VCAM on cell surface 245 Increased permeability 246 …”