Statins prevent endothelial cell activation induced by antiphospholipid (anti–β2-glycoprotein I) antibodies: Effect on the proadhesive and proinflammatory phenotype




To investigate the ability of statins, the inhibitors of the hydroxymethylglutaryl–coenzyme A reductase enzyme, to affect endothelial cell activation induced by anti–β2-glycoprotein I (anti-β2GPI) antibodies in vitro.


Human umbilical vein endothelial cell (HUVEC) activation was evaluated as U937 monocyte adhesion, E-selectin, and intercellular adhesion molecule 1 (ICAM-1) expression by cell enzyme-linked immunosorbent assay and as interleukin-6 (IL-6) messenger RNA (mRNA) expression by RNA protection assay. E-selectin–specific nuclear factor κB (NF-κB) DNA-binding activity was evaluated by the gel-shift assay. HUVECs were activated by polyclonal affinity-purified IgG, human monoclonal IgM anti-β2GPI antibodies, human recombinant IL-1β, tumor necrosis factor α, or lipopolysaccharide (LPS).


Fluvastatin reduced, in a concentration-dependent manner (1–10 μM), the adhesion of U937 to HUVECs and the expression of E-selectin and ICAM-1 induced by anti-β2GPI antibodies as well as by cytokines or LPS. Another lipophilic statin, simvastatin, display similar effects but to a lesser extent than fluvastatin. The inhibition of E-selectin expression exerted by fluvastatin was related to the impairment of NF-κB binding to DNA. Moreover, the drug attenuated the expression of IL-6 mRNA in HUVEC exposed to anti-β2GPI antibodies or cytokines. Incubation of HUVECs with mevalonate (100 μM), concomitantly with fluvastatin, greatly prevented the inhibitory effect of statin.


Endothelial activation mediated by anti-β2GPI antibody can be inhibited by statins. Because of the suggested role of endothelial cell activation in the pathogenesis of antiphospholipid syndrome (APS), our data provide, for the first time, a rationale for using statins as an additional therapeutic tool in APS.