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.
Statins prevent endothelial cell activation induced by antiphospholipid (anti-beta2-glycoprotein I) antibodies: effect on the proadhesive and proinflammatory phenotype / P.L. Meroni, E. Raschi, C. Testoni, A. Tincani, G. Balestrieri, R. Molteni, M.A. Khamashta, E. Tremoli, M. Camera. - In: ARTHRITIS AND RHEUMATISM. - ISSN 0004-3591. - 44:12(2001 Dec), pp. 2870-2878.
|Titolo:||Statins prevent endothelial cell activation induced by antiphospholipid (anti-beta2-glycoprotein I) antibodies: effect on the proadhesive and proinflammatory phenotype|
MERONI, PIERLUIGI (Primo)
TREMOLI, ELENA (Penultimo)
CAMERA, MARINA (Ultimo)
|Parole Chiave:||NF-kappa B ; Fatty Acids, Monounsaturated ; Antineoplastic Agents ; Humans ; Gene Expression ; Antibodies, Monoclonal ; Phenotype ; Indoles; E-Selectin; Lipopolysaccharides ; Glycoproteins ; Tumor Necrosis Factor-alpha ; Intercellular Adhesion Molecule-1 ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Endothelium, Vascular ; RNA, Messenger ; Interleukin-1 ; Cells, Cultured; Immunoglobulin G ; Umbilical Veins ; Interleukin-6 ; beta 2-Glycoprotein I ; Antibodies, Antiphospholipid; Immunoglobulin M ; Cell Adhesion ; U937 Cells|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||dic-2001|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1002/1529-0131(200112)44:12<2870::AID-ART475>3.0.CO;2-Y|
|Appare nelle tipologie:||01 - Articolo su periodico|