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Impaired endothelial barrier function resulting in increased vascular permeability is a characteristic vascular response in preeclampsia, a hypertensive and multiple systemic disorder of human pregnancy. During the last two decades, endothelial function in preeclampsia has been intensively studied and significant progress has been made in understanding the cellular and molecular bases of the altered endothelial cell response. In this review, we address the nature and mechanisms that are proposed to underlie the disturbed endothelial barrier function in preeclampsia and discuss the potential relevance of the endothelial cell responses to the initiation and/or progression of this vascular syndrome. Insights gained from the characterization of the endothelial cell phenotype assumed by the preeclamptic microvasculature may lead to novel therapeutic strategies for the management of this syndrome.

Background and Purpose The lymphatic system maintains tissue homeostasis by unidirectional lymph flow, maintained by tonic and phasic contractions within subunits, ‘lymphangions’. Here we have studied the effects of the inflammatory cytokine IL‐1β on tonic contraction of rat mesenteric lymphatic muscle cells (RMLMC). Experimental Approach We measured IL‐1β in colon‐conditioned media (CM) from acute (AC‐CM, dextran sodium sulfate) and chronic (CC‐CM, T‐cell transfer) colitis‐induced mice and corresponding controls (Con‐AC/CC‐CM). We examined tonic contractility of RMLMC in response to CM, the cytokines h‐IL‐1β or h‐TNF‐α (5, 10, 20 ng·mL−1), with or without COX inhibitors [TFAP (10−5 M), diclofenac (0.2 × 10−5 M)], PGE2 (10−5 M)], IL‐1‐receptor antagonist, Anakinra (5 μg·mL−1), or a selective prostanoid EP4 receptor antagonist, GW627368X (10−6 and 10−7 M). Key Results Tonic contractility of RMLMC was reduced by AC‐ and CC‐CM compared with corresponding control culture media, Con‐AC/CC‐CM. IL‐1β or TNF‐α was not found in Con‐AC/CC‐CM, but detected in AC‐ and CC‐CM. h‐IL‐1β concentration‐dependently decreased RMLMC contractility, whereas h‐TNF‐α showed no effect. Anakinra blocked h‐IL‐1β‐induced RMLMC relaxation, and with AC‐CM, restored contractility to RMLMC. IL‐1β increased COX‐2 protein and PGE2 production in RMLMC.. PGE2 induced relaxations in RMLMC, comparable to h‐IL‐1β. Conversely, COX‐2 and EP4 receptor inhibition reversed relaxation induced by IL‐1β. Conclusions and Implications The IL‐1β‐induced decrease in RMLMC tonic contraction was COX‐2 dependent, and mediated by PGE2. In experimental colitis, IL‐1β and tonic lymphatic contractility were causally related, as this cytokine was critical for the relaxation induced by AC‐CM and pharmacological blockade of IL‐1β restored tonic contraction.

Objective: To evaluate the risk of elective delivery of hospitalized patients with isolated mild preeclampsia with mature fetal lung profile compared with a cohort of patients who had preeclampsia with indicated delivery matched for gestational age.Study Design: Patients with mild preeclampsia requiring hospitalization between 34 and 37 weeks estimated gestational age were offered amniocentesis for assessment of fetal lung maturity. If fetal lung maturity was documented, patients were offered delivery. These cases were then compared with indicated or spontaneously delivered controls with preeclampsia matched for gestational age.Result: A total of 51 cases were identified and matched with 51 controls. Sixteen case neonates (31.4%) were admitted to neonatal intensive care unit compared with 21 controls (41.2%). Five cases (9.8%) in each group developed respiratory distress syndrome (RDS). Conclusion:Elective delivery of mild preeclampsia with mature lung profiles in the late preterm gestation is not without neonatal risks, including a 10% risk of RDS in this series.

Objective: Exaggerated inflammatory response occurs in preeclampsia. Preeclampsia is also associated with elevated endogenous digoxin-like factors (EDLFs). Clinical data suggest that Digibind (a polyclonal sheep digoxin binding Fab fragment) binds to EDLF and may have the potential to attenuate vasoconstriction and other clinical symptoms of preeclampsia. This study was undertaken to determine if Digibind could attenuate increased endothelial inflammatory response induced by tumor necrosis factor-a (TNFa).Study Design: Confluent endothelial cells were treated with TNFa at different concentrations with or without Digibind in culture. Endothelial adhesion molecule ICAM, VCAM and E-selectin expressions were determined by an immunoassay directly detected on the endothelial surface. Effects of Digibind on TNFa-induced extracellular signalregulated kinase and Na þ /K þ -ATPase expressions were also examined.Result: (1) TNFa induced dose-dependent increases in ICAM, VCAM and E-selectin expressions in endothelial cells; (2) Digibind could attenuate and reduce TNFa-induced upregulation of endothelial E-selectin, ICAM and VCAM expressions. The blocking effect was in a concentration dependent manner; (3) Digibind had no effects on TNFa-induced upregulation of extracellular signal-regulated kinase phosphorylation, but could block TNFa-induced downregulation of Na þ /K þ -ATPase b1 expression.Conclusion: Digibind may exert beneficial effects by preserving cell membrane Na þ /K þ -ATPase function and consequently to offset increased inflammatory response in endothelial cells.