Endothelium as a target for anti-phospholipid antibodies and for therapeutical intervention.
Endothelium activation seems to represent one of the pathogenic mechanisms that induce the trombophilic state of the anti-phospholipid syndrome. The rationale behind such a statement lies on the demonstration that: (a) the major antigen of the anti-phospholipid antibodies (beta 2 glycoprotein I) can be expressed on the endothelial cell membrane, (b) the endothelial beta 2 glycoprotein I offers suitable epitopes for circulating antibodies, (c) the binding of anti-beta 2 glycoprotein I antibodies is capable to induce the appearance of a pro-coagulant and pro-inflammatory phenotype. Both in vitro and in vivo experimental models support such a hypothesis. Although a classical vasculitic process cannot be found in the anti-phospholipid syndrome there is indirect evidence that endothelial activation/damage does occur also in vivo. The demonstration that hydroxymethylglutaryl Co-enzyme A reductase enzyme inhibitors (statins) can block endothelial cell activation induced by anti-beta 2 glycoprotein I antibodies as well as by pro-inflammatory cytokines offers new therapeutical approaches.
Meroni
Pier Luigi
PL
Allergy and Clinical Immunology Unit, Department of Internal Medicine, University of Milan, IRCCS Istituto Auxologico Italiano, Via L. Ariosto 13, 20145 Milan, Italy. pierluigi.meroni@unimi.it
Raschi
Elena
E
Testoni
Cinzia
C
D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D016736:Antiphospholipid Syndrome / Q000188:drug therapy*; D004730:Endothelium, Vascular / Q000187:drug effects*; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D008954:Models, Biological; D053482:beta 2-Glycoprotein I
D017152:Antibodies, Antiphospholipid; D006023:Glycoproteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D053482:beta 2-Glycoprotein I