Aikaterina Papayianni

Circulating vascular cell adhesion molecule–1 in pre-eclampsia, gestational hypertension, and normal pregnancy: Evidence of selective dysregulation of vascular cell adhesion molecule–1 homeostasis in pre-eclampsia

OBJECTIVE Our purpose was to investigate circulating levels of vascular cell adhesion molecule-1 in the peripheral and uteroplacental circulations during normotensive and hypertensive pregnancies. STUDY DESIGN This prospective observational study involved 2 patient groups. Group 1 consisted of 22 women with pre-eclampsia and 30 normotensive women followed up longitudinally through pregnancy and post partum. There were an additional 13 women with established gestational hypertension. Group 2 consisted of 20 women with established pre-eclampsia and 19 normotensive control subjects undergoing cesarean delivery. Plasma levels of vascular cell adhesion molecule-1 were measured in blood drawn from the antecubital vein (group 1) and from both the antecubital and uterine veins (group 2). Data were analyzed by analysis of variance. RESULTS In group 1 vascular cell adhesion molecule-1 levels did not change significantly throughout normal pregnancy and post partum. Women with established pre-eclampsia had increased vascular cell adhesion molecule-1 levels compared with the normotensive pregnancy group (P = .01). Vascular cell adhesion molecule-1 levels were not elevated in women with established gestational hypertension. In group 2 significantly higher levels of vascular cell adhesion molecule-1 were detected in the uteroplacental (P < .0001) and peripheral (P < .0001) circulations of pre-eclamptic women by comparison with normotensive women. In the pre-eclamptic group there was a tendency toward higher vascular cell adhesion molecule-1 levels in the peripheral circulation than in the uteroplacental circulation (P = .06). In contrast to vascular cell adhesion molecule-1, circulating levels of E-selectin and intercellular adhesion molecule-1, other major leukocyte adhesion molecules expressed by the endothelium, were not different in pre-eclamptic and normotensive pregnancies. CONCLUSION Established pre-eclampsia is characterized by selective dysregulation of vascular cell adhesion molecule-1 homeostasis. This event is not an early preclinical feature of pre-eclampsia, does not persist post partum, is not a feature of nonproteinuric gestational hypertension, and is not observed with other major leukocyte adhesion molecules. Induction of vascular cell adhesion molecule-1 expression in pre-eclampsia may contribute to leukocyte-mediated tissue injury in this condition or may reflect perturbation of other, previously unrecognized, functions of this molecule in pregnancy.

Potential vascular roles for lipoxins in the "stop programs" of host defense and inflammation.

Eicosanoids are oxygenated products of arachidonic acid or other related 20-carbon polyunsaturated fatty acids that modulate diverse biologic processes, including leukocyte recruitment and activation, hemostasis, blood flow, ion transport, smooth muscle contraction, mucous secretion, cell growth, and stimulus-response coupling. Inflammatory, thrombotic, and ischemic vascular events are complex multicellular responses that involve interactions of circulating blood cells with each other and with components of the vessel wall. Here, we review evidence that lipoxygenase-derived eicosanoids, specifically leukotrienes (LT) and lipoxins (LX), are generated within the vascular lumen during cell-cell interactions in inflammation and thrombosis. Transcellular biosynthetic pathways appear to be rich sources of LT and LX in these settings and may amplify the array and levels of lipid-derived mediators generated within a local vascular milieu. Cytokines and cell-cell adhesion can promote transcellular eicosanoid generation by amplifying pivotal enzymatic events in lipoxygenase biosynthetic pathways and facilitating transfer of relatively unstable lipophilic lipoxygenase-derived intermediates between cells. Leukotrienes are well-established proinflammatory mediators and stimuli for leukocyte recruitment and activation, plasma exudation, and smooth muscle contraction. Lipoxins, a more recent addition to the families of eicosanoids, inhibit LT-induced polymorphonuclear neutrophil (PMN) chemotaxis, adhesion to endothelial cells, diapedesis, vasoconstriction, and bronchoconstriction in several model systems and are potential modulators of LT bioactivity that may serve to limit PMN-mediated tissue injury in host defense, inflammation, ischemia-reperfusion, hemostasis, and other vascular events.