Inflammatory response and the endothelium

Anti phospholipid-mediated endothelium perturbation plays a role in anti phospholipid syndrome (APS)-associated vasculopathy. Anti phospholipid antibodies activate endothelium both in vitro and in vivo experimental models by inducing a pro-inflammatory/-coagutant phenotype; the antibodies recognize beta 2 glycoprotein I (beta 2GPI) on human endothelial cells (EC) from different parts of the vasculature. In spite of such large in vitro evidence, few studies have addressed the issue whether or not a comparable endothelial perturbation might be detectable in vivo. We investigated several indirect ex vivo parameters of endothelial dysfunction: plasma levels of soluble adhesion molecules (sADM), soluble thrombomodutin (sTM), von Willebrand factor (vWF) and tissue plasminogen activator (t-PA) by solid-phase assays. The study included: patients with primary anti phospholipid syndrome (n=32), with the syndrome secondary to non-active systemic lupus erythematosus (SLE, n=10), six patients with persistent antiphosphotipid positivity at medium/high titre without any clinical manifestation of the syndrome. Fifty-two age and sex matched healthy subjects have been enrolled as controls. In addition, circulating endothelial cells identified by flow cytometry and the brachial artery flow-mediated vasodilation (FMV) were evaluated in 26 patients (20 primary and 6 Lupus syndromes) and 30 healthy controls. Plasma levels of soluble adhesion molecules did not differ from controls, while a significant increase in von Willebrand factor titres (P < 0.05) was found. No significant difference was found regarding the number of circulating endothelial cells and flow-mediated vasoditation. As a whole, these findings do suggest that anti phospholipid antibodies per se are not able to support a full-blown endothetial perturbation in vivo. As shown in anti phospholipid syndrome experimental animal models, a two-hit hypothesis is suggested. (c) 2004 Elsevier Ltd. All rights reserved.