• 1
    Harris EN. Syndrome of the black swan. Br J Rheumatol 1987; 26: 3246.
  • 2
    Wilson WA, Gharavi AE, Koike T, Lockshin MD, Branch DW, Piette JC, et al. International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: report of an international workshop. Arthritis Rheum 1999; 42: 130911.
  • 3
    Pierangeli SS, Gharavi AE, Harris EN. Experimental thrombosis and antiphospholipid antibodies: new insights. J Autoimmun 2000; 15: 2417.
  • 4
    Pierangeli SS, Barker JH, Stikovac D, Ackerman D, Anderson G, Barquinero J, et al. Effect of human IgG antiphospholipid antibodies on an in vivo thrombosis model in mice. Thromb Haemost 1994; 17: 6704.
  • 5
    Pierangeli SS, Liu XW, Anderson GH, Barker JH, Harris EN. Induction of thrombosis in a mouse model by IgG, IgM and IgA immunoglobulins from patients with the antiphospholipid syndrome. Thromb Haemost 1995; 74: 13617.
  • 6
    Pierangeli SS, Liu XW, Anderson GH, Barker JH, Harris EN. Thrombogenic properties of murine anti-cardiolipin antibodies induced by β2 glycoprotein 1 and human IgG antiphospholipid antibodies. Circulation 1996; 94: 174651.
  • 7
    Sherer Y, Shoenfeld Y. Antiphospholipid syndrome: insight from animal models. Curr Opin Hematol 2000; 7: 3214.
  • 8
    Roubey RAS. Mechanisms of autoantiboby-mediated thrombosis. Lupus 1998; 7: S1149.
  • 9
    Meroni PL, Riboldi P. Pathogenic mechanisms mediating antiphospholipid syndrome. Curr Opin Rheumatol 2001; 13: 37782.
  • 10
    Esmon NL, Safa O, Smirnov M, Esmon CT. Antiphospholipid antibodies and the protein C pathway. J Autoimmun 2000; 15: 2215.
  • 11
    Campbell AL, Pierangeli SS, Wellhausen S, Harris EN. Comparison of the effect of anticardiolipin antibodies from patients with the antiphospholipid syndrome and with syphilis on platelet activation and aggregation. Thromb Haemost 1995; 73: 52934.
  • 12
    Espinola RG, Pierangeli SS, Gharavi AE, Harris EN. Hydroxychloroquine reverses platelet activation induced by human IgG antiphospholipid antibodies. Thromb Haemost 2002; 87: 51822.
  • 13
    Dobado-Berrios PM, Lopez-Pedreda C, Velazco F, Cuadrado MJ. The role of tissue factor in the antiphospholipid syndrome. Arthritis Rheum 2001; 44: 246776.
  • 14
    Meroni PL, Raschi E, Camera M, Testoni C, Nicoletti F, Tincani A, et al. Endothelial activation by aPL: a potential pathogenetic mechanism for the clinical manifestations of the syndrome. J Autoimmun 2000; 15: 23740.
  • 15
    Pierangeli SS, Espinola RG, Liu X, Harris EN. Thrombogenic effects of antiphospholipid antibodies are mediated by intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1, and P-selectin. Circ Res 2001; 88: 24550.
  • 16
    Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study. Lancet 1994; 344: 13839.
  • 17
    Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels: the long-term intervention with pravastatin in ischaemic disease (LIPID) study group. N Engl J Med 1998; 339: 134957.
  • 18
    Sacks FM, Pfeffer MA, Moye LA, Rouleau JL, Rutherford JD, Cole TG, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels: Cholesterol and Recurrent Events Trial investigators. N Engl J Med 1996; 335: 10019.
  • 19
    Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia: West of Scotland Coronary Prevention Study Group. N Engl J Med 1995; 333: 13017.
  • 20
    Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS (Air Force/Texas Coronary Atherosclerosis Prevention Study). JAMA 1998; 279: 161522.
  • 21
    Crouse JR, Byington RP, Furberg CD. HMG-CoA reductase inhibitor therapy and stroke risk reduction: an analysis of clinical trials data. Atherosclerosis 1998; 138: 1124.
  • 22
    Takemoto M, Liao JK. Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Arterioscler Thromb Vasc Biol 2001; 21: 17129.
  • 23
    Niwa S, Totsuka T, Hayashi S. Inhibitory effect of fluvastatin, an HMG-CoA reductase inhibitor, on the expression of adhesion molecules on human monocyte cell line. Int J Immunopharmacol 1996; 18: 66975.
  • 24
    Weitz-Schmidt G, Welzenbach K, Brinkmann V, Kamata T, Kallen J, Bruns C, et al. Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat Med 2001; 7: 68792.
  • 25
    Lefer AM, Campbell B, Shin YK, Scalia R, Hayward R, Lefer DJ. Simvastatin preserves the ischemic-reperfused myocardium in normocholesterolemic rat hearts. Circulation 1999; 100: 17884.
  • 26
    Scalia R, Gooszen ME, Jones SP, Hoffmeyer M, Rimmer DM III, Trocha SD, et al. Simvastatin exerts both anti-inflammatory and cardioprotective effects in apolipoprotein e-deficient mice. Circulation 2001; 103: 2598603.
  • 27
    Huhle G, Abletshauser C, Mayer N, Weidinger G, Harenberg J, Heene DL. Reduction of platelet activity markers in type II hypercholesterolemic patients by a HMG-CoA-reductase inhibitor. Thromb Res 1999; 95: 22934.
  • 28
    Aikawa M, Rabkin E, Sugiyama S, Voglic SJ, Fukumoto Y, Furukawa Y, et al. An HMG-CoA reductase inhibitor, cerivastatin, suppresses growth of macrophages expressing matrix metalloproteinases, and tissue factor in vivo, and in vitro. Circulation 2001; 103: 27683.
  • 29
    Colli S, Eligini S, Lalli M, Camera M, Paoletti R, Tremoli E. Vastatin inhibits tissue factor in cultured human macrophages. Arterioscler Thromb Vasc Biol 1997; 17: 26572.
  • 30
    Inoue I, Goto S, Mizotani K, Awata T, Mastunaga T, Kawai S, et al. Lipophilic HMG-CoA reductase inhibitor has an anti-inflammatory effect: reduction of mRNA levels for interleukin-1β, interleukin-6, cyclooxygenase-2, and p22phox by regulation of peroxisome proliferator-activated receptor α (PPARα) in primary endothelial cells. Life Sci 2000; 67: 86376.
  • 31
    Essig M, Nguyen G, Prie D, Escoubet B, Sraer JD, Friedlander G. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors increase fibrinolytic activity in rat aortic endothelial cells: role of geranylgeranylation and Rho proteins. Circ Res 1998; 83: 68390.
  • 32
    Bourcier T, Libby P. HMG CoA reductase inhibitors reduce plasminogen activator inhibitor-1 expression by human vascular smooth muscle and endothelial cells. Arterioscler Thromb Vasc Biol 2000; 20: 55662.
  • 33
    Kwak B, Mulhaupt F, Myit S, Mach F. Statins as a newly recognized type of immunomodulator. Nat Med 2000; 6: 1399402.
  • 34
    Grady D, Wenger NK, Herrington D, Khan S, Furberg C, Hunninghake D, et al, for the Heart and Estrogen/Progestin Replacement Study (HERS). Postmenopausal hormone therapy increases risk for venous thromboembolic disease. Ann Intern Med 2000; 132: 68996.
  • 35
    Ray JG, Mandami M, Tsuyuki RT, Anderson DR, Yeo EL, Laupacis A. Use of statins and the subsequent development of deep vein thrombosis. Arch Intern Med 2001; 161: 140510.
  • 36
    Meroni PL, Raschi E, Testoni C, Tincani A, Balestrieri G, Molteni R, et al. Statins prevent endothelial cell activation induced by antiphospholipid (anti–β2-glycoprotein I) antibodies: effect on the proadhesive and proinflammatory phenotype. Arthritis Rheum 2001; 44: 28708.
  • 37
    Pierangeli SS, Colden-Stanfield M, Liu X, Barker JH, Anderson GH, Harris EN. Antiphospholipid antibodies from antiphospholipid syndrome patients activate endothelial cells in vitro and in vivo. Circulation 1999; 99: 19972000.
  • 38
    Weir DM. Handbook of experimental immunology. Oxford, UK: Blackwell Scientific Publishers; 1986.
  • 39
    Liu X, Peter FW, Barker JH, Pierangeli SS, Harris EN, Anderson GL. Leukocyte-endothelium interaction in arterioles after ischemia and reperfusion. J Surg Res 1999; 87: 7784.
  • 40
    Langtry HD, Markham A. Fluvastatin. Drugs 1999; 57: 583606.
  • 41
    Kimura M, Kurose I, Russell J, Granger DN. Effects of fluvastatin on leukocyte endothelial cell adhesion in hypercholesterolemic rats. Arterioscler Thromb Vasc Biol 1997; 17: 15256.
  • 42
    Suzumura K, Ohashi N, Oka K, Tasuhara M, Narita H. Fluvastatin depresses the enhanced lipid peroxidation in vitamin E-deficient hamsters. Free Radic Res 2001; 35: 81523.
  • 43
    Jokubaitis LA. Development and pharmacology of fluvastatin. Br J Clin Pract Suppl 1996; 77A: 115.
  • 44
    Lennernas H, Fager G. Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors: similarities and differences. Clin Pharmacokinet 1997; 32: 40325.
  • 45
    Siekmeier R, Lattke P, Mix C, Park JW, Jaross W. Dose dependency of fluvastatin pharmacokinetics in serum determined by reversed phase HPLC. J Cardiovasc Pharmacol Ther 2001; 6: 13745.
  • 46
    Jankowski M, Vreys I, Wittevrongel C, Boon D, Vermylen J, Hoylaerts MF, et al. Thrombogenicity of β2-glycoprotein I-dependent antiphospholipid antibodies in a photochemically induced thrombosis model in the hamster. Blood 2003; 101: 15762.
  • 47
    Pober J, Cotran R. The role of endothelial cells in inflammation. Transplantation 1990; 50: 53744.
  • 48
    Olee T, Pierangeli SS, Handley HH, Novotny W, En J, Harris EN, et al. Generation and characterization of monoclonal IgG anticardiolipin antibodies from a patient with the antiphospholipid syndrome. Proc Natl Acad Sci U S A 1996; 93: 860611.
  • 49
    Simantov E, LaSala J, Lo SK, Gharavi AE, Sammaritano LR, Salmon JE, et al. Activation of cultured vascular endothelial cells by antiphospholipid antibodies. J Clin Invest 1995; 96: 22119.
  • 50
    Del Papa N, Guidali L, Sala A, Buccellati C, Khamashta MA, Ichikawa K, et al. Endothelial cells as target for antiphospholipid antibodies: human polyclonal and monoclonal anti–β2-glycoprotein I antibodies react in vitro with endothelial cells through adherent β2-glycoprotein I and induce endothelial activation. Arthritis Rheum 1997; 40: 55161.
  • 51
    Rosenson R, Tangney C. Antiatherothrombotic properties of statins. JAMA 1998; 279: 164350.
  • 52
    Corsini A, Bellosta S, Baetta R, Fumagalli R, Paoletti R, Bernini F. New insights into the pharmacodynamic and pharmacokinetics properties of statins. Pharmacol Ther 1999 84(3): 41328.
  • 53
    Camera M, Toschi V, Comparato C, Baetta R, Rossi F, Fuortes M, et al. Cholesterol-induced thrombogenicity of the vessel wall: inhibitory effect of fluvastatin. Thromb Haemost 2002; 87: 74855.
  • 54
    Meroni PL, Luzzana C, Ventura D. Anti-inflammatory and immunomodulating properties of statins: an additional tool for the therapeutic approach of systemic autoimmune diseases? Clin Rev Allergy Immunol 2002; 23: 26377.
  • 55
    Blanco-Colio LM, Tunon J, Martin-Ventura JL, Egiso J. Anti-inflammatory and immunomodulatory effects of statins. Kidney Int 2003; 63: 1223.
  • 56
    Fenton JW II, Shen GX, Minnear FL, Brezniak DV, Walenga JM, Bognacki JJ, et al. Statins induce hypothrombotic states? Clin Appl Thromb Hemost 2000; 6: 1821.
  • 57
    Porrecca E, DiFebbo C, Amore C, DiCastelnuovo A, Baccante G, Donati MB, et al. Effect of lipid-lowering treatment on factor VII profile in hyperlipidemic patients. Thromb Haemost 2000; 84: 78993.
  • 58
    Undas A, Brummel KE, Musial J, Mann KG, Szczeklik A. Simvastatin depresses blood clotting by inhibiting activation of prothrombin, factor V, and factor XIII and by enhancing factor Va inactivation. Circulation 2001; 103: 224853.
  • 59
    Gearing AJH, Newman W. Circulating adhesion molecules in disease. Immunol Today 1993; 14: 50612.
  • 60
    Furukawa S, Imai K, Matsubara T, Yone K, Yahi A, Okumura K, et al. Increased levels of circulating intercellular adhesion molecule 1 in Kawasaki disease. Arthritis Rheum 1992; 35: 6727.
  • 61
    Wang CR, Liu MF, Taai RT, Chuang CY, Cehn CY. Circulating intercellular adhesion molecule-1 and autoantibodies including anti-endothelial cell, anticardiolipin, and anti-neutrophil cytoplasma antibodies in patients with vasculitis. Clin Rheumatol 1993; 12: 37580.
  • 62
    Blann AD, Herrick A, Jayson MIV. Altered levels of soluble adhesion molecules in rheumatoid arthritis, vasculitis and systemic sclerosis. Br J Rheumatol 1995; 34: 8149.
  • 63
    Pall AA, Adu D, Drayson M, Taylor CM, Richards NT, Michael J. Circulating soluble adhesion molecules in systemic vasculitis. Nephrol Dial Transplant 1994; 9: 7704.
  • 64
    Barnett C Jr, Moore EE, Moore FA, Varl VS, Biffl WL. Soluble ICAM-1 (sICAM-1) provokes PMN release. J Surg Res 1996; 63: 610.
  • 65
    Khamashta MA, Cuadrado MJ, Mujic F, Taub NA, Hunt BM, Hughes GRV. The management of thrombosis in the antiphospholipid-antibody syndrome. N Engl J Med 1995; 332: 9937.
  • 66
    Krnic-Barrie S, O'Connor CR, Looney SW, Pierangeli SS, Harris EN. A retrospective review of 61 patients with antiphospholipid syndrome. Arch Intern Med 1997; 157: 21018.
  • 67
    Ginsburg KS, Liang MH, Newcomer L, Goldhaber SZ, Schur PH, Hennekens CH, et al. Anticardiolipin antibodies and the risk for ischemic stroke and venous thrombosis. Ann Intern Med 1992; 117: 9971002.