Top

Published in:

01-08-2012 | Original Research Paper

8-Isoprostane, prostaglandin E2, C-reactive protein and serum amyloid A as markers of inflammation and oxidative stress in antiphospholipid syndrome: a pilot study

Authors: Savino Sciascia, Dario Roccatello, Maria Tiziana Bertero, Debora Di Simone, Domenico Cosseddu, Antonella Vaccarino, Mario Bazzan, Daniela Rossi, Cesar Garcia-Fernandez, Leticia Ceberio, Stefania Stella, Elisa Menegatti, Simone Baldovino

Published in: Inflammation Research | Issue 8/2012

Abstract

Objective

To test the inflammation and oxidative stress hypothesis in antiphospholipid syndrome (APS) patients and to identify possible associations with clinical and laboratory features of the disease.

Methods

Serum amyloid A (SAA), C-reactive protein (CRP), 8-isoprostane and prostaglandin E2 (PGE) were assayed in the sera of 45 APS patients and then compared to control groups made up of 15 antiphospholipid antibody (aPL) negative patients with systemic lupus erythematosus, 15 aPL negative subjects with pregnancy-related morbidity, 15 aPL negative patients with thrombosis, 15 subjects with persistently positive aPL with no signs or symptoms of APS, and 15 healthy volunteers from among the hospital staff.

Results

APS patients showed significantly higher CRP (p = 0.01), SAA (p < 0.01), 8-isoprostane (p = 0.05) and PGE2 (p = 0.001) plasma levels as compared to controls. Among APS subjects, significantly higher 8-isoprostane and PGE2 levels were observed in patients with triple positivity for aPL (lupus anticoagulant, anticardiolipin and anti-beta2-glycoprotein I antibodies) compared to APS patients with single or double aPL positivity.

Conclusion

Both inflammation and oxidative stress, as measured by SAA, CRP, 8-isoprostane and PGE2, occur in APS and seem to be related to triple positivity for aPL.

Levi M, van der Poll T, Buller HR. Bidirectional relation between inflammation and coagulation. Circulation. 2004;109(22):2698–704.PubMedCrossRef

Sherer Y, Shoenfeld Y. Mechanisms of disease: atherosclerosis in autoimmune diseases. Nat Clin Pract Rheumatol. 2006;2(2):99–106.PubMedCrossRef

Jara LJ, Medina G, Vera-Lastra O, Shoenfeld Y. Atherosclerosis and antiphospholipid syndrome. Clin Rev Allergy Immunol. 2003;25(1):79–88.PubMedCrossRef

Soltesz P, Szekanecz Z, Kiss E, Shoenfeld Y. Cardiac manifestations in antiphospholipid syndrome. Autoimmun Rev. 2007;6(6):379–86.PubMedCrossRef

Ames PR, Margarita A, Sokoll KB, Weston M, Brancaccio V. Premature atherosclerosis in primary antiphospholipid syndrome: preliminary data. Ann Rheum Dis. 2005;64(2):315–7.PubMedCrossRef

Plazak W, Pasowicz M, Kostkiewicz M, Podolec J, Tomkiewicz-Pajak L, Musial J, et al. Influence of chronic inflammation and autoimmunity on coronary calcifications and myocardial perfusion defects in systemic lupus erythematosus patients. Inflamm Res. 2011;60(10):973–80.PubMedCrossRef

Ahmed K, Vianna JL, Khamashta MA, Hughes GR. IL-2, IL-6 and TNF levels in primary antiphospholipid syndrome. Clin Exp Rheumatol. 1992;10(5):503.PubMed

Forastiero RR, Martinuzzo ME, de Larranaga GF. Circulating levels of tissue factor and proinflammatory cytokines in patients with primary antiphospholipid syndrome or leprosy related antiphospholipid antibodies. Lupus. 2005;14(2):129–36.PubMedCrossRef

Hamid C, Norgate K, D’Cruz DP, Khamashta MA, Arno M, Pearson JD, et al. Anti-beta2GPI-antibody-induced endothelial cell gene expression profiling reveals induction of novel pro-inflammatory genes potentially involved in primary antiphospholipid syndrome. Ann Rheum Dis. 2007;66(8):1000–7.PubMedCrossRef

10.

Ames PR, Tommasino C, Brancaccio V, Ciampa A. C-reactive protein in primary antiphospholipid syndrome. J Rheumatol. 2007;34(3):650.PubMed

11.

Sailer T, Vormittag R, Pabinger I, Vukovich T, Lehr S, Quehenberger P, et al. Inflammation in patients with lupus anticoagulant and implications for thrombosis. J Rheumatol. 2005;32(3):462–8.PubMed

12.

Sidelmann JJ, Sjoland JA, Gram J, Bertelsen V, Mourits-Andersen T, Munster H, et al. Lupus anticoagulant is significantly associated with inflammatory reactions in patients with suspected deep vein thrombosis. Scand J Clin Lab Invest. 2007;67(3):270–9.PubMedCrossRef

13.

Miesbach W, Gokpinar B, Gilzinger A, Claus D, Scharrer I. Predictive role of hs-C-reactive protein in patients with antiphospholipid syndrome. Immunobiology. 2005;210(10):755–60.PubMedCrossRef

14.

Chang MK, Binder CJ, Torzewski M, Witztum JL. C-reactive protein binds to both oxidized LDL and apoptotic cells through recognition of a common ligand: phosphorylcholine of oxidized phospholipids. Proc Natl Acad Sci USA. 2002;99(20):13043–8.PubMedCrossRef

15.

Tabuchi M, Inoue K, Usui-Kataoka H, Kobayashi K, Teramoto M, Takasugi K, et al. The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis. J Lipid Res. 2007;48(4):768–81.PubMedCrossRef

16.

DE O’Connor ME, Coleman MC. Stereochemical course of the auto-oxidative cyclization of lipid hydroperoxides to prostaglandin-like signal peroxides. J Am Chem Soc. 1984;106:3577–84.CrossRef

17.

Morrow JD, Hill KE, Burk RF, Nammour TM, Badr KF, Roberts LJ 2nd. A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. Proc Natl Acad Sci USA. 1990;87(23):9383–7.PubMedCrossRef

18.

Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4(2):295–306.PubMedCrossRef

19.

Pengo V, Tripodi A, Reber G, Rand JH, Ortel TL, Galli M, et al. Update of the guidelines for lupus anticoagulant detection. Subcommittee on lupus anticoagulant/antiphospholipid antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost. 2009;7:1737–40.PubMedCrossRef

20.

Thiagarajan P, Pengo V, Shapiro S. The use of dilute Russell viper venom time for the diagnosis of lupus anticoagulants. Blood. 1986;68:869–74.PubMed

21.

Meroni PL, Borghi MO, Raschi E, Tedesco F. Pathogenesis of antiphospholipid syndrome: understanding the antibodies. Nat Rev Rheumatol. 2011;7(6):330–9.PubMedCrossRef

22.

Lambrianides A, Carroll CJ, Pierangeli SS, Pericleous C, Branch W, Rice J, et al. Effects of polyclonal IgG derived from patients with different clinical types of the antiphospholipid syndrome on monocyte signaling pathways. J Immunol. 2010;184(12):6622–8.PubMedCrossRef

23.

Agar C, van Os GM, Morgelin M, Sprenger RR, Marquart JA, Urbanus RT, et al. Beta2-glycoprotein I can exist in 2 conformations: implications for our understanding of the antiphospholipid syndrome. Blood. 2010;116(8):1336–43.PubMedCrossRef

24.

Raschi E, Testoni C, Bosisio D, Borghi MO, Koike T, Mantovani A, et al. Role of the MyD88 transduction signaling pathway in endothelial activation by antiphospholipid antibodies. Blood. 2003;101(9):3495–500.PubMedCrossRef

25.

Espinola RG, Liu X, Colden-Stanfield M, Hall J, Harris EN, Pierangeli SS. E-Selectin mediates pathogenic effects of antiphospholipid antibodies. J Thromb Haemost. 2003;1(4):843–8.PubMedCrossRef

26.

Shoenfeld Y, Gerli R, Doria A, Matsuura E, Cerinic MM, Ronda N, et al. Accelerated atherosclerosis in autoimmune rheumatic diseases. Circulation. 2005;112(21):3337–47.PubMedCrossRef

27.

Montuschi P, Barnes P, Roberts LJ 2nd. Insights into oxidative stress: the isoprostanes. Curr Med Chem. 2007;14(6):703–17.PubMedCrossRef

28.

Pengo V, Ruffatti A, Legnani C, Testa S, Fierro T, Marongiu F, et al. Incidence of a first thromboembolic event in asymptomatic carriers of high-risk antiphospholipid antibody profile: a multicenter prospective study. Blood. 2011;118(17):4714–8.PubMedCrossRef

29.

Ruffatti A, Tonello M, Cavazzana A, Bagatella P, Pengo V. Laboratory classification categories and pregnancy outcome in patients with primary antiphospholipid syndrome prescribed antithrombotic therapy. Thromb Res. 2009;123(3):482–7.PubMedCrossRef

30.

Pengo V, Biasiolo A, Pegoraro C, Cucchini U, Noventa F, Iliceto S. Antibody profiles for the diagnosis of antiphospholipid syndrome. Thromb Haemost. 2005;93(6):1147–52.PubMed

31.

Pengo V. APS–controversies in diagnosis and management, critical overview of current guidelines. Thromb Res. 2011;127(Suppl 3):S51–2.PubMedCrossRef

32.

Patrono C, FitzGerald GA. Isoprostanes: potential markers of oxidant stress in atherothrombotic disease. Arterioscler Thromb Vasc Biol. 1997;17(11):2309–15.PubMedCrossRef

33.

Morrow JD, Minton TA, Roberts LJ 2nd. The F2-isoprostane, 8-epi-prostaglandin F2 alpha, a potent agonist of the vascular thromboxane/endoperoxide receptor, is a platelet thromboxane/endoperoxide receptor antagonist. Prostaglandins. 1992;44(2):155–63.PubMedCrossRef

34.

Pratico D, Smyth EM, Violi F, FitzGerald GA. Local amplification of platelet function by 8-Epi prostaglandin F2alpha is not mediated by thromboxane receptor isoforms. J Biol Chem. 1996;271(25):14916–24.PubMedCrossRef

35.

Lynch SM, Morrow JD, Roberts LJ 2nd, Frei B. Formation of non-cyclooxygenase-derived prostanoids (F2-isoprostanes) in plasma and low density lipoprotein exposed to oxidative stress in vitro. J Clin Invest. 1994;93(3):998–1004.PubMedCrossRef

36.

Smith WL, Garavito RM, DeWitt DL. Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2. J Biol Chem. 1996;271(52):33157–60.PubMedCrossRef

37.

Wang Z, Ciabattoni G, Creminon C, Lawson J, Fitzgerald GA, Patrono C, et al. Immunological characterization of urinary 8-epi-prostaglandin F2 alpha excretion in man. J Pharmacol Exp Ther. 1995;275(1):94–100.PubMed

38.

Pratico D, FitzGerald GA. Generation of 8-epiprostaglandin F2alpha by human monocytes. Discriminate production by reactive oxygen species and prostaglandin endoperoxide synthase-2. J Biol Chem. 1996;271(15):8919–24.PubMedCrossRef

39.

Kloner RA, Przyklenk K, Whittaker P. Deleterious effects of oxygen radicals in ischemia/reperfusion. Resolved and unresolved issues. Circulation. 1989;80(5):1115–27.PubMedCrossRef

40.

Fabre JE, Nguyen M, Athirakul K, Coggins K, McNeish JD, Austin S, et al. Activation of the murine EP3 receptor for PGE2 inhibits cAMP production and promotes platelet aggregation. J Clin Invest. 2001;107(5):603–10.PubMedCrossRef

41.

Meroni PL, Raschi E, Testoni C, Tincani A, Balestrieri G, Molteni R, et al. Statins prevent endothelial cell activation induced by antiphospholipid (anti-beta2-glycoprotein I) antibodies: effect on the proadhesive and proinflammatory phenotype. Arthritis Rheum. 2001;44(12):2870–8.PubMedCrossRef

42.

Ferrara DE, Liu X, Espinola RG, Meroni PL, Abukhalaf I, Harris EN, et al. Inhibition of the thrombogenic and inflammatory properties of antiphospholipid antibodies by fluvastatin in an in vivo animal model. Arthritis Rheum. 2003;48(11):3272–9.PubMedCrossRef

43.

Proudfoot J, Barden A, Mori TA, Burke V, Croft KD, Beilin LJ, et al. Measurement of urinary F(2)-isoprostanes as markers of in vivo lipid peroxidation-A comparison of enzyme immunoassay with gas chromatography/mass spectrometry. Anal Biochem. 1999;272(2):209–15.PubMedCrossRef

Title: 8-Isoprostane, prostaglandin E2, C-reactive protein and serum amyloid A as markers of inflammation and oxidative stress in antiphospholipid syndrome: a pilot study
Authors: Savino Sciascia
Dario Roccatello
Maria Tiziana Bertero
Debora Di Simone
Domenico Cosseddu
Antonella Vaccarino
Mario Bazzan
Daniela Rossi
Cesar Garcia-Fernandez
Leticia Ceberio
Stefania Stella
Elisa Menegatti
Simone Baldovino
Publication date: 01-08-2012
Publisher: SP Birkhäuser Verlag Basel
Published in: Inflammation Research / Issue 8/2012
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-012-0468-0

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

8-Isoprostane, prostaglandin E2, C-reactive protein and serum amyloid A as markers of inflammation and oxidative stress in antiphospholipid syndrome: a pilot study

Abstract

Objective

Methods

Results

Conclusion

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Objective

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 8/2012

The anti-arthritic and anti-oxidative effect of NBD (6-nitro-1,3-benzodioxane) in adjuvant-induced arthritis (AIA) in rats

Carrageenan-induced transient inflammation in a rabbit knee model: molecular changes consistent with an early osteoarthritis phenotype

Inflammatory markers and bariatric surgery: a meta-analysis

AKT-mediated regulation of polarization in differentiated human neutrophil-like HL-60 cells

Chronic aspiration shifts the immune response from adaptive immunity to innate immunity in a murine model of asthma

Recombinant human endostatin inhibits adjuvant arthritis by down-regulating VEGF expression and suppression of TNF-α, IL-1β production

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page