Evaluating Serum Levels of Pentraxin-3, von Willebrand Factor and C-X-C Motif Chemokine Ligand 13 as Inflammatory Markers of Unstable Angina Pectoris

Keywords: C-X-C motif chemokine ligand 13, Global registry of acute coronary events risk score, Pentraxin-3, Stable angina, Thrombolysis in myocardial infarction risk score, Unstable angina, von willebrand factor


Unstable angina pectoris (USAP) is a complex condition in which widespread coronary inflammatory processes have important implications for clearer understanding of its pathogenesis and also its treatment. This study aimed at evaluating the diagnostic as well as prognostic value of serum inflammatory markers of pentraxin-3 (PTX-3), Von Willebrand Factor (vWf) and C-X-C Motif Chemokine Ligand 13 (CXCL13) in such patients. Out of sixty-nine patients, thirty-nine had USAP, thirty had stable angina pectoris (SAP), and thirty-nine were healthy controls. For all participants, serum PTX-3, vWf and CXCL13 levels were measured using ELISA. For each patient with USAP, the Thrombolysis in Myocardial Infarction (TIMI) and the scores of Global Registry of Acute Coronary Events (GRACE) were calculated to determine the severity of the disease. We, then, analyzed the relation of PTX-3, vWf and CXCL13 levels with TIMI and GRACE scores in patients with USAP. Serum PTX-3, vWf and CXCL13 levels were significantly higher in USAP group than those in either SAP or control groups (p˂0.001). Strong correlation was observed between CXCL13 level and TIMI risk score (p=0.019). In receiver operating characteristic (ROC) curves, area under the curve (AUC) values of PTX3, vWf and CXCL13 for detection of USAP were 0.755, 0.751, and 0.906, respectively. The levels of serum PTX3, vWf and CXCL13 increased in patients with USAP. The notable correlation implied that CXCL13 might be a sensitive and specific biomarker for the diagnosis of USAP as well as its severity. It might also show additional diagnostic values when measured in combination with vWf.

Author Biography

Hassan Nikoueinejad, Department of Immunology, Baqiyatallah University of Medical Sciences, Tehran, Iran AND Nephrology and Urology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran




1. Braunwald E, Jones RH, Mark DB, Brown J, Brown L, Cheitlin MD,et al. Diagnosing and managing unstable angina. Agency for Health Care Policy and Research. Circulation 1994;90(1):613-22.
2. Pokras R. Detailed diagnoses and procedures for patients discharged from short-stay hospitals, United States; 1985. 1987.
3. Hamm CW, Bleifeld W. Unstable angina: current concepts of medical management. Cardiovascular drugs and therapy 1988;2(3):333-9.
4. Falk E. Unstable angina with fatal outcome: dynamic coronary thrombosis leading to infarction and/or sudden death. Autopsy evidence of recurrent mural thrombosis with peripheral embolization culminating in total vascular occlusion. Circulation 1985;71(4):699-708.
5. Makki N, Brennan TM, Girotra S. Acute coronary syndrome. J Intensive Care Med 2015;30(4):186-200.
6. Antman EM, Cohen M, Bernink PJ, McCabe CH, Horacek T, Papuchis G, et al. The TIMI risk score for unstable angina/non–ST elevation MI: a method for prognostication and therapeutic decision making. JAMA 2000;284(7):835-42.
7. Tang EW, Wong C-K, Herbison P. Global Registry of Acute Coronary Events (GRACE) hospital discharge risk score accurately predicts long-term mortality post acute coronary syndrome. Am Heart J 2007;153(1):29-35.
8. Llamas M-Á, Aller M-Á, Marquina D, Nava M-P, Arias J. Bacterial translocation to mesenteric lymph nodes increases in chronic portal hypertensive rats. Dig Dis Sci 2010;55(8):2244-54.
9. Investigators FI. Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomized multicentre study. Fragmin and fast Revascularization during InStabilily in Coronary artery disease investigators. Lancet 1999;354(9180):708-15.
10. Eagle KA, Lim MJ, Dabbous OH, Pieper KS, Goldberg RJ, Van de Werf F, et al. A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month postdischarge death in an international registry. JAMA 2004;291(22):2727-33.
11. Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl J Med 1992;326(4):242-50.
12. Lusis AJ. Atherosclerosis. Nature 2000;407(6801):233-41.
13. Bottazzi B, Vouret-Craviari V, Bastone A, De Gioia L, Matteucci C, Peri G, et al. Multimer Formation and Ligand Recognition by the Long Pentraxin PTX3 similarities and differences with the short pentraxins C-reactive protein and serum amyloid P component. J Biol Chem 1997;272(52):32817-23.
14. Feys HB, Van Aelst B, Devloo R, Vandekerckhove P, Compernolle V. The contribution of von Willebrand factor-GPIbα interactions to persistent aggregate formation in apheresis platelet concentrates. Vox Sang 2016;110(4):344-51.
15. Goto S, Sakai H, Goto M, Ono M, Ikeda Y, Handa S, et al. Enhanced shear-induced platelet aggregation in acute myocardial infarction. Circulation 1999;99(5):608-13.
16. Montalescot G, Philippe F, Ankri A, Vicaut E, Bearez E, Poulard JE, et al. Early increase of von Willebrand factor predicts adverse outcome in unstable coronary artery disease: beneficial effects of enoxaparin. Circulation 1998;98(4):294-9.
17. Moreth K, Brodbeck R, Babelova A, Gretz N, Spieker T, Zeng-Brouwers J, et al. The proteoglycan biglycan regulates expression of the B cell chemoattractant CXCL13 and aggravates murine lupus nephritis. J Clin Invest 2010;120(12):4251-72.
18. Weber C. Chemokines in atherosclerosis, thrombosis, and vascular biology. Arterioscler Thromb Vasc Biol 2008;28(11):1896.
19. Fox KA, Goodman SG, Klein W, Brieger D, Steg PG, Dabbous O, et al. Management of acute coronary syndromes. Variations in practice and outcome. Findings from the Global Registry of Acute Coronary Events (GRACE). Eur Heart J 2002;23(15):1177-89.
20. Gruberg L, Mehran R, Waksman R, Dangas G, Fuchs S, Wu H, et al. Creatine kinase-MB fraction elevation after percutaneous coronary intervention in patients with chronic renal failure. Am J Cardiol 2001;87(12):1356-60.
21. Casula M, Montecucco F, Bonaventura A, et al. Update on the role of Pentraxin 3 in atherosclerosis and cardiovascular diseases. Vascul Pharmacol 2017;99:1-12.
22. Inoue K, Sugiyama A, Reid PC, et al. Establishment of a high sensitivity plasma assay for human pentraxin3 as a marker for unstable angina pectoris. Arterioscler Thromb Vasc Biol 2007;27(1):161-7.
23. Grundy SM, Hansen B, Smith SC, Cleeman JI, Kahn RA. Clinical management of metabolic syndrome: report of the American Heart Association/National Heart, Lung, and Blood Institute/American Diabetes Association conference on scientific issues related to management. Circulation 2004;109(4):551-6.
24.Napoleone E, Di Santo A, Bastone A, Peri G, et al. Long pentraxin PTX3 upregulates tissue factor expression in human endothelial cells: a novel link between vascular inflammation and clotting activation. Arterioscler Thromb Vasc Biol 2002;22(5):782-7.
25. Peri G, Introna M, Corradi D, Iacuitti G, Signorini S, Avanzini F, et al. PTX3, A prototypical long pentraxin, is an early indicator of acute myocardial infarction in humans. Circulation 2000;102(6):636-41.
26. Kume N, Mitsuoka H, Hayashida K, Tanaka M. Pentraxin 3 as a biomarker for acute coronary syndrome: comparison with biomarkers for cardiac damage. J Cardiol 2011;58(1):38-45.
27. Matsui S, Ishii J, Kitagawa F, Kuno A, Hattori K, Ishikawa M, et al. Pentraxin 3 in unstable angina and non-ST-segment elevation myocardial infarction. Atherosclerosis 2010;210(1):220-5.
28. Büyükkaya E, Karakaş MF, Kurt M, Akcay AB, Büyükkaya S, Karakaş E, et al. The serum pentraxin-3 is elevated in patients with cardiac syndrome X. Turk Kardiyol Dern Ars 2013; 41(4):290-5.
29. Kimura S, Nakamura S, Nakagama S, Hayasaka K, Misawa T, Mizusawa M, et al. P2367The impact of systemic pentraxin-3 values on coronary plaque components by optical coherence tomography and outcomes in patients with stable angina pectoris. Eur Heart J2017; 38(suppl_1):ehx502.P2367-ehx502.P.
30.Liu H, Guo X, Yao K, et al. Pentraxin-3 Predicts Long-Term Cardiac Events in Patients with Chronic Heart Failure. Biomed Res Int 2015; 2015:817615.
31. Latini R, Maggioni AP, Peri G, Gonzini L, Lucci D, Mocarelli P, et al. Prognostic significance of the long pentraxin PTX3 in acute myocardial infarction. Circulation 2004; 110(16):2349-54.
32. Sonneveld MA, de Maat MP, Leebeek FW. Von Willebrand factor and ADAMTS13 in arterial thrombosis: a systematic review and meta-analysis. Blood Rev 2014; 28(4):167-78.
33. Tiong WN, Sim EUH, Fong AYY, Ong TK. Early detection of C-reactive protein and von Willebrand factor levels in Malaysian patients with acute coronary syndrome. J Cardiovasc Dis Res 2013; 4(1):3-6.
34. Nogami K, Shima M, Nishiya K, et al. A novel mechanism of factor VIIIprotection by von Willebrand factor from activated protein C-catalyzed inactivation. Blood 2002;99(11):3993-8.
35. Brinkman HJ, van Mourik JA, Mertens K. Persistent factor VIII-dependent factor X activation on endothelial cells is independent of von Willebrand factor. Blood Coagul Fibrinolysis 2008;19(3):190-6.
36. Bobescu E, Covaciu A, Rus H, et al. Correlation of Cardiovascular Risk Factors and Biomarkers With Platelet Reactivity in Coronary Artery Disease. Am J Ther 2018.
37. Gragnano F, Golia E, Natale F, et al. Von Willebrand Factor and Cardiovascular Disease: From a Biochemical Marker to an Attractive Therapeutic Target. Curr Vasc Pharmacol 2017;15(5):404-415.
38. Montalescot G, Collet JP, Choussat R, Ankri A, Thomas D. A rise of troponin and/or von Willebrand factor over the first 48 h is associated with a poorer 1-year outcome in unstable angina patients. Int J Cardiol 2000;72(3):293-4.
39. Montalescot G, Philippe F, Ankri A. For the French Investigation of the ESSENCE Trial. Early increase of von Willebrand factor predicts adverse outcome in unstable coronary artery disease: beneficial effects of enoxaparin. Circulation 1998;98:287.
40. Montalescot G, Collet JP, Lison L, et al. Effects of various anticoagulant treatments on von Willebrand factor release in unstable angina. J Am CollCardiol 2000; 36(1):110-4.
41. Damås JK, Smith C, Øie E, Fevang B, Halvorsen B, Wæhre T, et al. Enhanced expression of the homeostatic chemokines CCL19 and CCL21 in clinical and experimental atherosclerosis: possible pathogenic role in plaque destabilization. ArteriosclerThrombVascBiol 2007; 27(3):614-20.
42. Smedbakken LM, Halvorsen B, Daissormont I, Ranheim T, Michelsen AE, Skjelland M, et al. Increased levels of the homeostatic chemokine CXCL13 in human atherosclerosis–potential role in plaque stabilization. Atherosclerosis 2012; 224(1):266-73.
43. Pearson TA, Mensah GA, Alexander RW, Anderson JL, Cannon RO, Criqui M, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 2003; 107(3):499-511.
How to Cite
Raygan F, Mohammadi H, Etminan A, Sehat M, Nikoueinejad H. Evaluating Serum Levels of Pentraxin-3, von Willebrand Factor and C-X-C Motif Chemokine Ligand 13 as Inflammatory Markers of Unstable Angina Pectoris. Iran J Allergy Asthma Immunol. 18(2):200-208.
Original Article(s)