Statins prevent endothelial cell activation induced by antiphospholipid (anti-beta(2)-glycoprotein I) antibodies - Effect on the proadhesive and proinflammatory phenotype

TY - JOUR

T1 - Statins prevent endothelial cell activation induced by antiphospholipid (anti-beta(2)-glycoprotein I) antibodies - Effect on the proadhesive and proinflammatory phenotype

AU - Meroni, P L

AU - Raschi, E

AU - Testoni, C

AU - Tincani, A

AU - Balestrieri, G

AU - Molteni, R

AU - Khamashta, M A

AU - Tremoli, E

AU - Camera, M

PY - 2001

Y1 - 2001

N2 - Objective. To investigate the ability of statins, the inhibitors of the hydroxymethylglutaryl-coenzyme A reductase enzyme, to affect endothelial cell activation induced by anti-beta (2)-glycoprotein I (anti-beta (2)GPI) antibodies in vitro. Methods. 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 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-beta (2)GPI antibodies, human recombinant IL-1 beta, tumor necrosis factor alpha, or lipopolysaccharide (LPS). Results. Fluvastatin reduced, in a concentration-dependent manner (1-10 muM), the adhesion of U937 to HUVECs and the expression of E-selectin and ICAM-1 induced by anti-beta (2)GPI 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-beta (2)GPI antibodies or cytokines. Incubation of HUVECs with mevalonate (100 muM), concomitantly with fluvastatin, greatly prevented the inhibitory effect of statin. Conclusion. Endothelial activation mediated by anti-beta (2)GPI 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.

AB - Objective. To investigate the ability of statins, the inhibitors of the hydroxymethylglutaryl-coenzyme A reductase enzyme, to affect endothelial cell activation induced by anti-beta (2)-glycoprotein I (anti-beta (2)GPI) antibodies in vitro. Methods. 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 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-beta (2)GPI antibodies, human recombinant IL-1 beta, tumor necrosis factor alpha, or lipopolysaccharide (LPS). Results. Fluvastatin reduced, in a concentration-dependent manner (1-10 muM), the adhesion of U937 to HUVECs and the expression of E-selectin and ICAM-1 induced by anti-beta (2)GPI 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-beta (2)GPI antibodies or cytokines. Incubation of HUVECs with mevalonate (100 muM), concomitantly with fluvastatin, greatly prevented the inhibitory effect of statin. Conclusion. Endothelial activation mediated by anti-beta (2)GPI 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.

M3 - Conference paper

SN - 1529-0131

VL - 44

SP - 2870

EP - 2878

JO - Arthritis & Rheumatism

JF - Arthritis & Rheumatism

IS - 12

T2 - 64th Annual Scientific Meeting of the American-College-of-Rheumatology

Y2 - 1 January 2001

ER -