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.