Top

Published in:

01-08-2018 | IM - ORIGINAL

Nuclear factor kappa B in patients with a history of unstable angina: case re-opened

Authors: Chiara Mozzini, Ulisse Garbin, Chiara Stranieri, Giulia Salandini, Giancarlo Pesce, Anna Maria Fratta Pasini, Luciano Cominacini

Published in: Internal and Emergency Medicine | Issue 5/2018

Abstract

This study aims at assessing NF-kB activity in unstable angina (UA) patients free of symptoms after a 1 year follow-up (1YFU). Plasma oxidized low-density lipoproteins (oxLDL), circulating NF-kB, Interleukin 6 (IL-6) and Interleukin 1β (IL-1β), high-sensitivity C-reactive protein (hs-CRP), as markers of oxidative stress and inflammation and plasma double-stranded DNA (ds-DNA), as marker of Neutrophil Extracellular Traps (NETs), were measured in 23 of the previously enrolled 27 UA patients. These measurements were compared to the UA data at baseline, and then compared to the data derived from the stable angina (SA) and controls (C) enrolled in our previous study (we demonstrated that UA had higher levels of NF-kB compared to SA and C). After a 1YFU, UA patients show a significant decrease in NF-kB, IL-6, hs-CRP, oxLDL, and ds-DNA plasma levels (p < 0.001) and in IL-1β and White Blood Cells (WBC) (p < 0.005), without differences in lipid and glucose assessment. If compared to SA and C, UA after a 1YFU have higher levels of NF-kB, IL-6, ds-DNA, WBC, and oxLDL compared to C (p < 0.001), but only IL-6 is higher than SA (p < 0.001). No differences are found in lipid and glucose assessment. After a 1YFU, patients with a history of UA improve their oxidative and inflammatory status, such as the levels of circulating ds-DNA, without achieving the status of C. They become comparable to SA subjects. This study provides new insight on the multiple and apparently contradictory facets of NF-kB in UA and on its possible role as mediator in NETs’ formation.

Mathers CD, Loncar D (2006) Projection of global mortality and burden of disease from 2002 to 2030. PLoS Med 3:2011–2030. https://doi.org/10.1371/journal.pmed.0030442 CrossRef

Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC) (2016) 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Eur Heart J 37:267–315. https://doi.org/10.1093/eurheartj/ehv320 CrossRef

Thygesen K, Mair J, Giannitsis E, Mueller C, Lindahl B, Blankenberg S, Huber K, Plebani M, Biasucci LM, Tubaro M, Collinson P, Venge P, Hasin Y, Galvani M, Koenig W, Hamm C, Alpert JS, Katus H, Jaffe AS (2012) How to use high-sensitivity cardiac troponins in acute cardiac care. Eur Heart J 33:2252–2257. https://doi.org/10.1093/eurheartj/ehs154 CrossRefPubMed

Braunwald E, Morrow DA (2013) Unstable angina: is it time for a requiem? Circulation 127:2452–2457. https://doi.org/10.1161/CIRCULATIONAHA.113.001258 CrossRefPubMed

Mockel M, Searle J, Hamm C, Slagman A, Blankenberg S, Huber K, Katus H, Liebetrau C, Muller C, Muller R, Peitsmeyer P, von Recum J, Tajsic M, Vollert JO, Giannitsis E (2015) Early discharge using single cardiac troponin and copeptin testing in patients with suspected acute coronary syndrome (ACS): a randomized, controlled clinical process study. Eur Heart J 36:369–376. https://doi.org/10.1093/eurheartj/ehu178 CrossRefPubMed

Kumar A, Takada Y, Borick AM, Aggarwal BB (2004) Nuclear factor kappa B: its role in health and disease. J Mol Med 82:434–448. https://doi.org/10.1007/s00109-004-0555-y CrossRefPubMed

Mitchell S, Vargas J, Hoffmann A (2016) Signaling via the NF-kB system. Syst Biol Med 8:227–241. https://doi.org/10.1002/wsbm.1331 CrossRef

Hayden MS, Ghosh S (2008) Shared principles in NF-kappa B signaling. Cell 132:344–362. https://doi.org/10.1016/j.cell.2008.01.020 CrossRefPubMed

Gordon JW, Shaw JA, Kirshenbaum LA (2011) Multiple facets of NF-kB in the heart: to be or not to NF-kB. Circ Res 108:1122–1132. https://doi.org/10.1161/CIRCRESAHA.110.226928 CrossRefPubMed

10.

Karin M, Lin A (2002) NF-kB at the crossroads of life and death. Nat Immun 3:221–227. https://doi.org/10.1038/ni0302-221 CrossRef

11.

Suzuki N, Kamataki A, Yamaki J, Homma Y (2008) Characterization of circulating DNA in healthy human plasma. Clin Chim Acta 387:55–59. https://doi.org/10.1016/j.cca.2007.09.001 CrossRefPubMed

12.

Swarup V, Rajeswari A (2007) Circulating (cell-free) nucleic acids—a promising non-invasive tool for early detection of several human diseases. FEBS Lett 581:795–799. https://doi.org/10.1016/j.febslet.2007.01.051 CrossRefPubMed

13.

Cui M, Fan M, Jing R, Wang H, Qin J, Sheng H, Wang Y, Wu X, Zhang L, Zhu J, Ju S (2013) Cell-free circulating DNA: a new biomarker for the acute coronary syndrome. Cardiology 124(2):76–84. https://doi.org/10.1159/000345855 CrossRefPubMed

14.

Chang CP, Chia RH, Wu TL, Tsao KC, Sun CF, Wu JT (2003) Elevated cell-free serum DNA detected in patients with myocardial infarction. Clin Chim Acta 327(1–2):95–101CrossRefPubMed

15.

Destouni A, Vrettou C, Antonatos D, Chouliaras G, Traeger-Synodinos J, Patsilinakos S, Kitsiou-Tzeli S, Tsigas D, Kanavakis E (2009) Cell-free DNA levels in acute myocardial infarction patients during hospitalization. Acta Cardiol 64(1):51–57. https://doi.org/10.2143/AC.64.1.2034362 CrossRefPubMed

16.

Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A (2004) Neutrophil extracellular traps kill bacteria. Science 303(5663):1532–1535. https://doi.org/10.1126/science.1092385 CrossRefPubMed

17.

Fuchs TA, Abed U, Goosmann C, Hurwitz R, Schulze I, Wahn V, Weinrauch Y, Brinkmann V, Zychlinsky A (2007) Novel cell death program leads to neutrophil extracellular traps. J Cell Biol 176(2):231–241. https://doi.org/10.1083/jcb.200606027 CrossRefPubMedPubMedCentral

18.

Marcos V, Zhou Z, Yildirim AO, Bohla A, Hector A, Vitkov L, Wiedenbauer E-M, Krautgartner WD, Stoiber W, Belohradsky BH (2010) CXCR2 mediates NADPH oxidase-independent neutrophil extracellular trap formation in cystic fibrosis airway inflammation. Nat Med 16:1018–1023. https://doi.org/10.1038/nm.2209 CrossRefPubMed

19.

Sangaletti S, Tripodo C, Chiodoni C, Guarnotta C, Cappetti B, Casalini P, Piconese S, Parenza M, Guiducci C, Vitali C (2012) Neutrophil extracellular traps mediate transfer of cytoplasmic neutrophil antigens to myeloid dendritic cells toward ANCA induction and associated autoimmunity. Blood 120:3007–3018. https://doi.org/10.1182/blood-2012-03-416156 CrossRefPubMed

20.

Brinkmann V, Zychlinsky A (2012) Neutrophil extracellular traps: is immunity the second function of chromatin? J Cell Biol 198:773–783. https://doi.org/10.1083/jcb.201203170 CrossRefPubMedPubMedCentral

21.

Demers M, Krause DS, Schatzberg D, Martinod K, Voorhees JR, Fuchs TA, Scadden DT, Wagner DD (2012) Cancers predispose neutrophils to release extracellular DNA traps that contribute to cancer-associated thrombosis. Proc Natl Acad Sci USA 109:13076–13081. https://doi.org/10.1073/pnas.1200419109 CrossRefPubMedPubMedCentral

22.

Demers M, Wagner DD (2014) NETosis: a new factor in tumour progression and cancer-associated thrombosis. Semin Thromb Haemost 40(3):277–283. https://doi.org/10.1055/s-0034-1370765 CrossRef

23.

Borissoff JI, Joosen IA, Versteylen MO, Brill A, Fuchs TA, Savchenko AS, Gallant M, Martinod K, Ten Cate H, Hofstra L, Crijns HJ, Wagner DD, Kietselaer BL (2013) Elevated levels of circulating DNA and chromatin are independently associated with severe coronary atherosclerosis and a prothrombotic state. Arterioscler Thromb Vasc Biol 33(8):2032–2040. https://doi.org/10.1161/ATVBAHA.113.301627 CrossRefPubMedPubMedCentral

24.

Megens RT, Vijayan S, Lievens D, Döring Y, van Zandvoort MA, Grommes J, Weber C, Soehnlein O (2012) Presence of luminal neutrophil extracellular traps in atherosclerosis. Thromb Haemost 107(3):597–598. https://doi.org/10.1160/TH11-09-0650 CrossRefPubMed

25.

De Boer OJ, Li X, Teeling P, Mackaay C, Ploegmakers HJ, van der Loos CM, Daemen MJ, de Winter RJ, van der Wal AC (2013) Neutrophils, neutrophil extracellular traps and interleukin-17 associate with the organisation of thrombi in acute myocardial infarction. Thromb Haemost 109(2):290–297. https://doi.org/10.1160/TH12-06-0425 CrossRefPubMed

26.

Mangold A, Alias S, Scherz T, Hofbauer T, Jakowitsch J, Panzenböck A, Simon D, Laimer D, Bangert C, Kammerlander A, Mascherbauer J, Winter MP, Distelmaier K, Adlbrecht C, Preissner KT, Lang IM (2015) Coronary neutrophil extracellular trap burden and deoxyribonuclease activity in ST-elevation acute coronary syndrome are predictors of ST-segment resolution and infarct size. Circ Res 116(7):1182–1192. https://doi.org/10.1161/CIRCRESAHA.116.304944 CrossRefPubMed

27.

Mozzini C, Garbin U, Fratta Pasini AM, Cominacini L (2016) An exploratory look at NETosis in atherosclerosis. Intern Emerg Med. https://doi.org/10.1007/s11739-016-1543-2 CrossRefPubMed

28.

Cominacini L, Anselmi M, Garbin U, Fratta Pasini A, Stranieri C, Fusaro M, Nava C, Agostoni P, Keta D, Zardini P, Sawamura T, Lo Cascio V (2005) Enhanced plasma levels of oxidized low-density lipoprotein increase circulating nuclear factor-kappa B activation in patients with unstable angina. J Am Coll Cardiol 46:799–806. https://doi.org/10.1016/j.jacc.2005.05.063 CrossRefPubMed

29.

Fratta Pasini AM, Anselmi M, Garbin U, Franchi E, Stranieri C, Nava MC, Boccioletti V, Vassanelli L, Cominacini L (2007) Enhanced levels of oxidized low density lipoprotein prime monocytes to cytokine overproduction via upregulation of CD14 and Toll-like receptor 4 in unstable angina. Arterioscler Thromb Vasc Biol 27:1991–1997. https://doi.org/10.1161/ATVBAHA.107.142695 CrossRefPubMed

30.

Lindorfer MA, Schuman TA, Craig ML, Martin EN, Taylor RP (2001) A bispecific dsDNA monoclonal antibody construct for clearance of anti-dsDNA IgG in systemic lupus erythematosus. J Immunol Methods 248(1–2):125–138CrossRefPubMed

31.

Li Y, Ha T, Gao X, Kelley J, Williams DI, Browder IW, Kao RI, Li C (2004) NF-kB activation is required for the development of cardiac hypertrophy in vivo. Am J Physiol 287:H1712–H1721. https://doi.org/10.1152/ajpheart.00124.2004 CrossRef

32.

Frantz S, Hu K, Bayer B, Gerondakis S, Strottmann J, Adamek A, Ertl G, Bauersachs J (2006) Absence of NF-kB subunit p50 improves heart failure after myocardial infarction. FASEB J 20:1918–1920. https://doi.org/10.1096/fj.05-5133fje CrossRefPubMed

33.

Dhingra R, Shaw JA, Aviv Y, Kirshenbaum LA (2010) Dichotomous actions of NF-kappaB signaling pathways in heart. J Cardiovasc Transl Res 4:344–354. https://doi.org/10.1007/s12265-010-9195-5 CrossRef

34.

You M, Ku PT, Hrdlikova R, Bose HR (1997) Ch-IAP-1 member of the inhibitor of apoptosis protein family is a mediator of the antiapoptotic activity of the v-Rel oncoprotection. Mol Cell Biol 17:7328–7341CrossRefPubMedPubMedCentral

35.

Chu ZL, Mc Kinsey TA, Liu L, Gentry JJ, Malim MH, Ballard DW (1997) Suppression of tumour necrosis factor induced death by inhibitor of apoptosis c-IAP2 is under NF-kB control. Proc Natl Acad Sci 94:10057–10062CrossRefPubMedPubMedCentral

36.

Wang CY, Mayo MW, Korneluk RG, Goeddel DV, Baldwin AS (1998) NF-kB antiapoptosis: induction of TRAF1 and TRAF2 and cIAP1 and c-IAP2 to suppress caspase-8 activation. Science 281:1680–1683CrossRefPubMed

37.

Papa S, Bubici C, Zazzeroni F, Pham CG, Kuntzen C, Knabb JR, Dean K, Franzoso G (2006) The NF- kB- mediated control of JNK cascade in the antagonism of programmed cell death in health and disease. Cell Death Differ 13:712–729. https://doi.org/10.1038/sj.cdd.4401865 CrossRefPubMed

38.

Beere HM (2004) The stress of dying: the role of heat shock proteins in the regulation of apoptosis. J Cell Sci 117:2641–2651. https://doi.org/10.1242/jcs.01284 CrossRefPubMed

39.

Beere HM (2005) Death versus survival: functional interaction between the apoptotic and stress-inducible heat shock protein pathways. J Clin Investig 115:2633–2639. https://doi.org/10.1172/JCI26471 CrossRefPubMedPubMedCentral

40.

Valen G, Hansson GK, Dumitrescu A, Vaage J (2000) Unstable angina activates myocardial heat shock protein 72, endothelial nitric oxide synthase and transcription factor NF kappa B and AP-1. Cardiovasc Res 47:49–56CrossRefPubMed

41.

Czibik G, Wu Z, Berne G, Tarkka M, Vaage J, Laurikka J, Jarvinen O, Valen G (2008) Human adaptation to ischemia by preconditioning or unstable angina: involvement of nuclear factor kappa B, but not hypoxia-inducible factor 1 alpha in the heart. Eur J Cardiothorac Surg 34:976–984. https://doi.org/10.1016/j.ejcts.2008.07.066 CrossRefPubMed

42.

Tahepold P, Vaage J, Starkopt J, Valen G (2003) Hyperoxia elicits myocardial protection through a nuclear factor kappa B-dependent mechanism in the rat heart. J Thorac Cardiovasc Surg 125:650–660. https://doi.org/10.1067/mtc.2003.36 CrossRefPubMed

43.

Xuan YT, Tang XL, Banerjee S, Takano H, Li RC, Han H, Qlu Y, Li JJ, Bolli R (1999) Nuclear factor kappa B plays an essential role in the late phase of ischemic preconditioning in conscious rabbits. Circ Res 84:1095–1109CrossRefPubMed

44.

Misra A, Haudek SB, Knuefermann P, Vallejo JG, Chen ZJ, Michael LH, Sivasubramanian N, Olson EN, Entman ML, Mann DI (2003) Nuclear factor kappa B protects the adult cardiac myocyte against ischemia-induced apoptosis in a murine model of acute myocardial infarction. Circulation 108:3075–3078. https://doi.org/10.1161/01.CIR.0000108929.93074.0B CrossRefPubMed

45.

Libby P (2013) Mechanisms of acute coronary syndromes and their implications for therapy. N Engl J Med 368:2004–2013. https://doi.org/10.1056/NEJMra1216063 CrossRefPubMed

46.

Buffon A, Basucci LM, Liuzzo G (2002) Widespread coronary inflammation in unstable angina. N Engl J Med 347:5–12. https://doi.org/10.1056/NEJMoa012295 CrossRefPubMed

47.

Bogaty P, Boyer L, Simard S, Dauwe F, Dupuis R, Verret B, Huynh T, Betrand F, Dagenais GR, Brophy JM (2008) The RISCA (Recurrence and Inflammation in the Acute Coronary Syndromes) Study. Clinical utility of C-reactive protein measured ad admission, hospital discharge and 1 month later to predict outcome in patients with acute coronary syndrome. J Am Coll Cardiol 51(24):2339–2346. https://doi.org/10.1016/j.jacc.2008.03.019 CrossRefPubMed

48.

Liuzzo G, Biasucci LM, Gallimore JR (1994) The prognostic value of C-reactive protein and serum amyloid A protein in severe unstable angina. N Eng J Med 331:417–424. https://doi.org/10.1056/NEJM199408183310701 CrossRef

49.

Biasucci LM, Liuzzo G, Grillo RL (1999) Elevated levels of C-reactive protein at discharge in patients with unstable angina predict recurrent instability. Circulation 99:855–860CrossRefPubMed

50.

Liuzzo G, Santamaria M, Biasucci LM, Narducci M, Colafrancesco V, Porto A, Brugaletta S, Pinnelli M, Rizzello V, Maseri A, Crea F (2007) Persistent activation of Nuclear Factor Kappa-B signaling pathway in patients with unstable angina and elevated levels of C-reactive protein. J Am Coll Cardiol 49:185–194. https://doi.org/10.1016/j.jacc.2006.07.071 CrossRefPubMed

51.

Lapponi MJ, Carestia A, Landoni VI, Rivadeneyra L, Etulain J, Negrotto S, Pozner RG, Schattner M (2013) Regulation of neutrophil extracellular trap formation by anti-inflammatory drugs. J Pharmacol Exp Ther 345(3):430–437. https://doi.org/10.1124/jpet.112.202879 CrossRefPubMed

52.

Yin MJ, Yamamoto Y, Gaynor RB (1998) The anti-inflammatory agent aspirin and salicylate inhibit the activity of IkB kinase beta. Nature 396:77–80. https://doi.org/10.1038/23948 CrossRefPubMed

53.

Mc Donald PP, Bald A, Cassatella MA (1997) Activation of the NF-kappaB pathway by inflammatory stimuli in human neutrophils. Blood 89:3421–3433

54.

Massberg S, Grahl L, von Bruehl ML (2010) Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases. Nat Med 16:887–896. https://doi.org/10.1038/nm.2184 CrossRefPubMed

55.

Ross R (1999) Atherosclerosis: an inflammatory disease. N Engl J Med 340:115–126CrossRefPubMed

56.

Ridker PM, Rifai N, Stampfer MJ, Hennekens CH (2000) Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 101:1767–1772CrossRefPubMed

57.

Libby P, Ridker PM, Hansson GK (2009) Inflammation in atherosclerosis: from pathophysiology to practice. J Am Coll Cardiol 54:2129–2138. https://doi.org/10.1016/j.jacc.2009.09.009 CrossRefPubMedPubMedCentral

58.

Biasucci LM, Vitelli A, Liuzzo G, Altamura S, Caligiuri G, Monaco C, Rebuzzi AG, Ciliberto G, Maseri A (1996) Elevated levels of Interleukin-6 in unstable angina. Circulation 94:874–877CrossRefPubMed

59.

Dinarello CA (2000) The role of the interleukin-1-receptor antagonist in blocking inflammation mediated by interleukin-1. N Engl J Med 343:732–734. https://doi.org/10.1056/NEJM200009073431011 CrossRefPubMed

60.

Dinarello CA (2009) Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol 27:519–550. https://doi.org/10.1146/annurev.immunol.021908.132612 CrossRefPubMed

61.

Sims JE, Smith DE (2010) The IL-1 family: regulators of immunity. Nat Rev Immunol 10:89–102. https://doi.org/10.1038/nri2691 CrossRefPubMed

62.

Stutz A, Golenbock DT, Latz E (2009) Inflammasomes: too big to miss. J Clin Invest 119:3502–3511. https://doi.org/10.1172/JCI40599 CrossRefPubMedPubMedCentral

63.

Ogura Y, Sutterwala FS, Flavell RA (2006) The inflammasome: first line of the immune response to cell stress. Cell 126:659–662. https://doi.org/10.1016/j.cell.2006.08.002 CrossRefPubMed

64.

Rajama K, Lappalainen J, Oorni K (2010) Cholesterol crystals activate the NLRP3 inflammasome in human macrophages: a novel link between cholesterol metabolism and inflammation. PLoS ONE 5:e11765. https://doi.org/10.1371/journal.pone.0011765 CrossRef

65.

Ridker P, Howard C, Walter V, Everett B, Libby P, Hensen J, Thuren T (2012) Effects of interleukin-1 inhibition with canakinumab on hemoglobin A1c, lipids, C-reactive protein, interleukin-6, and fibrinogen: a phase IIb randomized, placebo-controlled trial. Circulation 126:2739–2748. https://doi.org/10.1161/CIRCULATIONAHA.112.122556 CrossRefPubMed

66.

Warnatsch A, Ioannou M, Wang Q, Papayannopoulos V (2015) Neutrophil extracellular traps license macrophages for cytokine production in atherosclerosis. Science 349(6245):316–320. https://doi.org/10.1126/science.aaa8064 CrossRefPubMedPubMedCentral

67.

Joshi MB, Lad A, Prasad AB, Balakrishnan A, Ramachandra L, Satyamoorthy K (2013) High glucose modulates IL-6 mediated immune homeostasis through impeding neutrophil extracellular trap formation. FEBS Lett 587:2241–2246. https://doi.org/10.1016/j.febslet.2013.05.053 CrossRefPubMed

68.

Ikeda U, Ito T, Shimada K (2001) Interleukin-6 and acute coronary syndrome. Clin Cardiol 24(11):701–704CrossRefPubMed

69.

Rus HG, Vlaicu R, Niculescu F (1996) Interleukin-6 and interleukin-8 protein and gene expression in human arterial atherosclerotic wall. Atherosclerosis 127(2):263–271CrossRefPubMed

70.

Manten A, de Winter RJ, Minnema MC, ten Cate H, Lijmer JG, Adams R, Peters RJ, van Deventer SJ (1998) Procoagulant and proinflammatory activity in acute coronary syndromes. Cardiovasc Res 40(2):389–395CrossRefPubMed

71.

Wang XH, Liu SQ, Wang YL, Jin Y (2014) Correlation of serum high-sensitivity C-reactive protein and interleukin-6 in patients with acute coronary syndrome. Genet Mol Res 13(2):4260–4266CrossRefPubMed

72.

Lai CL, Ji YR, Liu XH, Xing JP, Zhao JQ (2011) Relationship between coronary atherosclerosis plaque characteristics and high sensitivity C-reactive proteins, interleukin-6. Chin Med J (Eng) 124(16):2452–2456

73.

Van Lenten BJ, Hama SY, de Beer FC, Stafforini DM, McIntyre TM, Prescott SM, La Du BN, Fogelman AM, Navab M (1995) Anti-inflammatory HDL becomes pro-inflammatory during the acute phase response. Loss of protective effect of HDL against LDL oxidation in aortic wall cell cocultures. J Clin Investig 96(6):2758–2767. https://doi.org/10.1172/JCI118345 CrossRefPubMedPubMedCentral

74.

Neumann FJ, Ott I, Marx N, Luther T, Kenngott S, Gawaz M, Kotzsch M, Schömig A (1997) Effect of human recombinant interleukin-6 and interleukin-8 on monocyte procoagulant activity. Arterioscler Thromb Vasc Biol 17(12):3399–3405CrossRefPubMed

75.

Gwechenberger M, Mendoza LH, Youker KA, Frangogiannis NG, Smith CW, Michael LH, Entman ML (1999) Cardiac myocytes produce interleukin-6 in culture and in viable border zone of reperfused infarctions. Circulation 99(4):546–551CrossRefPubMed

76.

Caselli C, De Graaf MA, Lorenzoni V, Rovai D, Marinelli M, Del Ry S, Giannessi D, Bax JJ, Neglia D, Schlte AJ (2015) HDL cholesterol, leptin and interleukin-6 predict high risk coronary anatomy assessed by CT angiography in patients with stable chest pain. Atherosclerosis 241(1):55–61. https://doi.org/10.1016/j.atherosclerosis.2015.04.811 CrossRefPubMed

77.

Koyama K, Yoneyama K, Mitarai T, Ishibashi Y, Takahashi E, Kongoji K, Harada T, Akashi YJ (2015) Association between inflammatory biomarkers and thin-cap fibroatheroma detected by optical coherence tomography in patients with coronary heart disease. Arch Med Sci 11(3):505–512. https://doi.org/10.5114/aoms.2015.52352 CrossRefPubMedPubMedCentral

78.

Plutzki J (2001) Inflammatory pathways in atherosclerosis and acute coronary syndromes. Am J Cardiol 88(8A):10K–15KCrossRef

79.

Brasier AR (2010) The nuclear factor-kB—interleukin-6 signalling pathway mediating vascular inflammation. Cardiovasc Res 86:211–218. https://doi.org/10.1093/cvr/cvq076 CrossRefPubMedPubMedCentral

80.

Libermann TA, Baltimore D (1990) Activation of interleukin-6 gene expression through the NF-kappa B transcription factor. Mol Cell Biol 10(5):2327–2334CrossRefPubMedPubMedCentral

81.

Lippi G, Sanchis-Gomar F, Cervellin G (2015) Cell-free DNA for diagnosing myocardial infarction: not ready for prime time. Clin Chem Lab Med 53(12):1895–1901. https://doi.org/10.1515/cclm-2015-0252 CrossRefPubMed

82.

Tonello S, Rizzia M, Migliario M, Rocchetti V, Renò F (2017) Low concentrations of neutrophil extracellular traps induce proliferation in human keratinocytes via NF-kB activation. J Dermatol Sci 88:110–116CrossRefPubMed

Title: Nuclear factor kappa B in patients with a history of unstable angina: case re-opened
Authors: Chiara Mozzini
Ulisse Garbin
Chiara Stranieri
Giulia Salandini
Giancarlo Pesce
Anna Maria Fratta Pasini
Luciano Cominacini
Publication date: 01-08-2018
Publisher: Springer International Publishing
Published in: Internal and Emergency Medicine / Issue 5/2018
Print ISSN: 1828-0447
Electronic ISSN: 1970-9366
DOI: https://doi.org/10.1007/s11739-018-1885-z

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

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

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits

STEP AAG HeroTeaserCollection image/© Tarek / Generated with AI / Stock.adobe.com, ACC 2024 Pediatric and Congenital Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Pulmonary Vascular Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 Valvular Heart Disease: Year in Review/© 2024 American College of Cardiology, ACC 2024 HF and Cardiomyopathies: Year in Review/© 2024 American College of Cardiology, Woman out walking/© Seventyfour / stock.adobe.com (symbolic image with model), Woman checking smartwatch /© saltdium / stock.adobe.com (symbolic image with model), Cardiac catheterization/© Damian / stock.adobe.com

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 5/2018

Daylight saving time, circadian rhythms, and cardiovascular health

Aristolochia, a nephrotoxic herb, still surfs on the Web, 15 years later

Drug-eluting stents vs. bare metal stents in elderly patients

Oxidative stress and inflammation: new molecular targets for cardiovascular diseases

Author Correction: Toxic alcohol diagnosis and management: an emergency medicine review

Emergency Department influenza vaccination campaign allows increasing influenza vaccination coverage without disrupting time interval quality indicators

Highlights from the ACC 2024 Congress

ACC 2024 Congress Coverage