Statins prevent endothelial cell activation induced by antiphospholipid (anti-beta2-glycoprotein I) antibodies: effect on the proadhesive and proinflammatory phenotype

Arthritis Rheum. 2001 Dec;44(12):2870-8. doi: 10.1002/1529-0131(200112)44:12<2870::aid-art475>;2-y.


Objective: To investigate the ability of statins, the inhibitors of the hydroxymethylglutaryl-coenzyme A reductase enzyme, to affect endothelial cell activation induced by anti-beta2-glycoprotein I (anti-beta2GPI) antibodies in vitro.

Methods: Human umbilical vein endothelial cell (HUVEC) activation was evaluated as U937 monocyte adhesion, E-selectin, and intercellular adhesion molecule I (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 kappaB (NF-kappaB) DNA-binding activity was evaluated by the gel-shift assay. HUVECs were activated by polyclonal affinity-purified IgG, human monoclonal IgM anti-beta2GPI antibodies, human recombinant IL-1beta, tumor necrosis factor alpha, or lipopolysaccharide (LPS).

Results: Fluvastatin reduced, in a concentration-dependent manner (1-10 microM), the adhesion of U937 to HUVECs and the expression of E-selectin and ICAM-1 induced by anti-beta2GPI antibodies as well as by cytokines or LPS. Another lipophilic statin, simvastatin, displayed 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-kappaB binding to DNA. Moreover, the drug attenuated the expression of IL-6 mRNA in HUVEC exposed to anti-beta2GPI antibodies or cytokines. Incubation of HUVECs with mevalonate (100 microM), concomitantly with fluvastatin, greatly prevented the inhibitory effect of statin.

Conclusion: Endothelial activation mediated by anti-beta2GPI 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Antiphospholipid / pharmacology*
  • Antibodies, Monoclonal / pharmacology
  • Antineoplastic Agents / pharmacology
  • Cell Adhesion / immunology
  • Cells, Cultured
  • E-Selectin / genetics
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / immunology
  • Fatty Acids, Monounsaturated / pharmacology*
  • Fluvastatin
  • Gene Expression / drug effects
  • Gene Expression / immunology
  • Glycoproteins / immunology*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Immunoglobulin G / pharmacology
  • Immunoglobulin M / pharmacology
  • Indoles / pharmacology*
  • Intercellular Adhesion Molecule-1 / genetics
  • Interleukin-1 / pharmacology
  • Interleukin-6 / genetics
  • Lipopolysaccharides / pharmacology
  • NF-kappa B / metabolism
  • Phenotype
  • RNA, Messenger / analysis
  • Tumor Necrosis Factor-alpha / pharmacology
  • U937 Cells
  • Umbilical Veins / cytology
  • beta 2-Glycoprotein I


  • Antibodies, Antiphospholipid
  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • E-Selectin
  • Fatty Acids, Monounsaturated
  • Glycoproteins
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Immunoglobulin G
  • Immunoglobulin M
  • Indoles
  • Interleukin-1
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • beta 2-Glycoprotein I
  • Intercellular Adhesion Molecule-1
  • Fluvastatin