title: Inflammatory response and the endothelium.
abstract: Antiphospholipid-mediated endothelium perturbation plays a role in antiphospholipid syndrome (APS)-associated vasculopathy. Antiphospholipid antibodies activate endothelium both in vitro and in vivo experimental models by inducing a pro-inflammatory/-coagulant phenotype; the antibodies recognize beta2 glycoprotein I (beta2GPI) 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 thrombomodulin (sTM), von Willebrand factor (vWF) and tissue plasminogen activator (t-PA) by solid-phase assays. The study included: patients with primary antiphospholipid syndrome (n=32), with the syndrome secondary to non-active systemic lupus erythematosus (SLE, n=10), six patients with persistent antiphospholipid 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 vasodilation. As a whole, these findings do suggest that antiphospholipid antibodies per se are not able to support a full-blown endothelial perturbation in vivo. As shown in antiphospholipid syndrome experimental animal models, a two-hit hypothesis is suggested.
authors.affiliation: Department of Internal Medicine, University of Milan, Istituto Auxologico Italiano, Milan, Italy. pierluigi.meroni@unimi.it
authors.forename: P L
authors.initials: PL
authors.lastname: Meroni
authors.forename: M O
authors.initials: MO
authors.lastname: Borghi
authors.forename: E
authors.initials: E
authors.lastname: Raschi
authors.forename: D
authors.initials: D
authors.lastname: Ventura
authors.forename: P C
authors.initials: PC
authors.lastname: Sarzi Puttini
authors.forename: F
authors.initials: F
authors.lastname: Atzeni
authors.forename: L
authors.initials: L
authors.lastname: Lonati
authors.forename: G
authors.initials: G
authors.lastname: Parati
authors.forename: A
authors.initials: A
authors.lastname: Tincani
authors.forename: D
authors.initials: D
authors.lastname: Mari
authors.forename: F
authors.initials: F
authors.lastname: Tedesco
mesh_terms: D016736:Antiphospholipid Syndrome / Q000097:blood / Q000473:pathology; D002448:Cell Adhesion; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D008177:Lupus Vulgaris / Q000473:pathology; D008297:Male; D008954:Models, Biological; D010641:Phenotype; D018180:Thrombomodulin / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000097:blood; D053482:beta 2-Glycoprotein I; D014841:von Willebrand Factor / Q000096:biosynthesis
chemical_list: D006023:Glycoproteins; D018180:Thrombomodulin; D053482:beta 2-Glycoprotein I; D014841:von Willebrand Factor; D010959:Tissue Plasminogen Activator