Coronary leukocyte activation in relation to progression of coronary artery disease

Abstract

Leukocyte activation has been linked to atherogenesis, but there is little in vivo evidence for its role in the progression of atherosclerosis. We evaluated the predictive value for progression of coronary artery disease (CAD) of leukocyte activation markers in the coronary circulation. Monocyte and neutrophil CD11b, neutrophil CD66b expression and intracellular neutrophil myeloperoxidase (MPO) in the coronary arteries were determined by flow cytometry in patients undergoing coronary angiography. The primary outcome included fatal and nonfatal myocardial infarction or arterial vascular intervention due to unstable angina pectoris. In total 99 subjects who were included, 70 had CAD at inclusion (26 patients had single-vessel disease, 18 patients had two-vessel disease and 26 patients had three-vessel disease). The median follow-up duration was 2242 days (interquartile range: 2142–2358). During follow-up, 13 patients (13%) developed progression of CAD. Monocyte CD11b, neutrophil CD11b and CD66b expression and intracellular MPO measured in blood obtained from the coronary arteries were not associated with the progression of CAD. These data indicate that coronary monocyte CD11b, neutrophil CD11b and CD66b expression and intracellular MPO do not predict the risk of progression of CAD.

Keywords

coronary artery disease / inflammation / integrin / myeloperoxidase / leukocyte activation

References

[1] Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, McQueen M, Budaj A, Pais P, Varigos J, Lisheng L; INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004; 364(9438): 937–952PMID:15364185

[2] Libby P. Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol 2012; 32(9): 2045–2051

[3] Friedman GD, Klatsky AL, Siegelaub AB. The leukocyte count as a predictor of myocardial infarction. N Engl J Med 1974; 290(23): 1275–1278

[4] Danesh J, Whincup P, Walker M, Lennon L, Thomson A, Appleby P, Gallimore JR, Pepys MB. Low grade inflammation and coronary heart disease: prospective study and updated meta-analyses. BMJ 2000; 321(7255): 199–204

[5] Muscari A, Bozzoli C, Puddu GM, Sangiorgi Z, Dormi A, Rovinetti C, Descovich GC, Puddu P. Association of serum C3 levels with the risk of myocardial infarction. Am J Med 1995; 98(4): 357–364

[6] Alipour A, van Oostrom AJHHM, Izraeljan A, Verseyden C, Collins JM, Frayn KN, Plokker TWM, Elte JWF, Castro Cabezas M. Leukocyte activation by triglyceride-rich lipoproteins. Arterioscler Thromb Vasc Biol 2008; 28(4): 792–797

[7] van Oostrom AJHHM, Rabelink TJ, Verseyden C, Sijmonsma TP, Plokker HWM, De Jaegere PPT, Cabezas MC. Activation of leukocytes by postprandial lipemia in healthy volunteers. Atherosclerosis 2004; 177(1): 175–182

[8] Gower RM, Wu H, Foster GA, Devaraj S, Jialal I, Ballantyne CM, Knowlton AA, Simon SI. CD11c/CD18 expression is upregulated on blood monocytes during hypertriglyceridemia and enhances adhesion to vascular cell adhesion molecule-1. Arterioscler Thromb Vasc Biol 2011; 31(1): 160–166

[9] Sampson MJ, Davies IR, Brown JC, Ivory K, Hughes DA. Monocyte and neutrophil adhesion molecule expression during acute hyperglycemia and after antioxidant treatment in type 2 diabetes and control patients. Arterioscler Thromb Vasc Biol 2002; 22(7): 1187–1193

[10] Motton DD, Keim NL, Tenorio FA, Horn WF, Rutledge JC. Postprandial monocyte activation in response to meals with high and low glycemic loads in overweight women. Am J Clin Nutr 2007; 85(1): 60–65

[11] Mazzone A, Ricevuti G. Leukocyte CD11/CD18 integrins: biological and clinical relevance. Haematologica 1995; 80(2): 161–175

[12] Yoon J, Terada A, Kita H. CD66b regulates adhesion and activation of human eosinophils. J Immunol 2007; 179(12): 8454–8462

[13] Barouch FC, Miyamoto K, Allport JR, Fujita K, Bursell SE, Aiello LP, Luscinskas FW, Adamis AP. Integrin-mediated neutrophil adhesion and retinal leukostasis in diabetes. Invest Ophthalmol Vis Sci 2000; 41(5): 1153–1158

[14] Simpson PJ, Todd RF 3rd, Fantone JC, Mickelson JK, Griffin JD, Lucchesi BR. Reduction of experimental canine myocardial reperfusion injury by a monoclonal antibody (anti-Mo1, anti-CD11b) that inhibits leukocyte adhesion. J Clin Invest 1988; 81(2): 624–629

[15] Chavakis T, Bierhaus A, Al-Fakhri N, Schneider D, Witte S, Linn T, Nagashima M, Morser J, Arnold B, Preissner KT, Nawroth PP. The pattern recognition receptor (RAGE) is a counterreceptor for leukocyte integrins: a novel pathway for inflammatory cell recruitment. J Exp Med 2003; 198(10): 1507–1515

[16] Ducker TP, Skubitz KM. Subcellular localization of CD66, CD67, and NCA in human neutrophils. J Leukoc Biol 1992; 52(1): 11–16

[17] Nauseef WM. Myeloperoxidase in human neutrophil host defence. Cell Microbiol 2014; 16(8): 1146–1155

[18] Mazzone A, De Servi S, Mazzucchelli I, Fossati G, Gritti D, Canale C, Cusa C, Ricevuti G. Increased expression of CD11b/CD18 on phagocytes in ischaemic disease: a bridge between inflammation and coagulation. Eur J Clin Invest 1997; 27(8): 648–652

[19] de Servi S, Mazzone A, Ricevuti G, Mazzucchelli I, Fossati G, Angoli L, Valentini P, Boschetti E, Specchia G. Expression of neutrophil and monocyte CD11B/CD18 adhesion molecules at different sites of the coronary tree in unstable angina pectoris. Am J Cardiol 1996; 78(5): 564–568

[20] De Servi S, Mazzone A, Ricevuti G, Mazzucchelli I, Fossati G, Gritti D, Angoli L, Specchia G. Clinical and angiographic correlates of leukocyte activation in unstable angina. J Am Coll Cardiol 1995; 26(5): 1146–1150

[21] Mazzone A, De Servi S, Ricevuti G, Mazzucchelli I, Fossati G, Pasotti D, Bramucci E, Angoli L, Marsico F, Specchia G, . Increased expression of neutrophil and monocyte adhesion molecules in unstable coronary artery disease. Circulation 1993; 88(2): 358–363PMID:8101771

[22] Berliner S, Rogowski O, Rotstein R, Fusman R, Shapira I, Bornstein NM, Prochorov V, Roth A, Keren G, Eldor A, Zeltser D. Activated polymorphonuclear leukocytes and monocytes in the peripheral blood of patients with ischemic heart and brain conditions correspond to the presence of multiple risk factors for atherothrombosis. Cardiology 2000; 94(1): 19–25

[23] Biasucci LM, D’Onofrio G, Liuzzo G, Zini G, Monaco C, Caligiuri G, Tommasi M, Rebuzzi AG, Maseri A. Intracellular neutrophil myeloperoxidase is reduced in unstable angina and acute myocardial infarction, but its reduction is not related to ischemia. J Am Coll Cardiol 1996; 27(3): 611–616

[24] Fasching P, Veitl M, Rohac M, Streli C, Schneider B, Waldhäusl W, Wagner OF. Elevated concentrations of circulating adhesion molecules and their association with microvascular complications in insulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1996; 81(12): 4313–4317

[25] Joussen AM, Murata T, Tsujikawa A, Kirchhof B, Bursell SE, Adamis AP. Leukocyte-mediated endothelial cell injury and death in the diabetic retina. Am J Pathol 2001; 158(1): 147–152

[26] Alipour A, Ribalta J, Njo TL, Janssen HW, Birnie E, van Miltenburg AJM, Elte JWF, Castro Cabezas M. Trans-vessel gradient of myeloperoxidase in coronary artery disease. Eur J Clin Invest 2013; 43(9): 920–925

[27] Naruko T, Ueda M, Haze K, van der Wal AC, van der Loos CM, Itoh A, Komatsu R, Ikura Y, Ogami M, Shimada Y, Ehara S, Yoshiyama M, Takeuchi K, Yoshikawa J, Becker AE. Neutrophil infiltration of culprit lesions in acute coronary syndromes. Circulation 2002; 106(23): 2894–2900

[28] Morrow DA, Sabatine MS, Brennan ML, de Lemos JA, Murphy SA, Ruff CT, Rifai N, Cannon CP, Hazen SL. Concurrent evaluation of novel cardiac biomarkers in acute coronary syndrome: myeloperoxidase and soluble CD40 ligand and the risk of recurrent ischaemic events in TACTICS-TIMI 18. Eur Heart J 2008; 29(9): 1096–1102

[29] Rana JS, Arsenault BJ, Després JP, Côté M, Talmud PJ, Ninio E, Wouter Jukema J, Wareham NJ, Kastelein JJP, Khaw KT, Boekholdt SM. Inflammatory biomarkers, physical activity, waist circumference, and risk of future coronary heart disease in healthy men and women. Eur Heart J 2011; 32(3): 336–344

[30] Grammer TB, Fuchs D, Boehm BO, Winkelmann BR, Maerz W. Neopterin as a predictor of total and cardiovascular mortality in individuals undergoing angiography in the Ludwigshafen Risk and Cardiovascular Health study. Clin Chem 2009; 55(6): 1135–1146

[31] Sulo G, Vollset SE, Nygård O, Midttun Ø, Ueland PM, Eussen SJPM, Pedersen ER, Tell GS. Neopterin and kynurenine-tryptophan ratio as predictors of coronary events in older adults, the Hordaland Health Study. Int J Cardiol 2013; 168(2): 1435–1440

[32] Arai M, Lefer DJ, So T, DiPaula A, Aversano T, Becker LC. An anti-CD18 antibody limits infarct size and preserves left ventricular function in dogs with ischemia and 48-hour reperfusion. J Am Coll Cardiol 1996; 27(5): 1278–1285

[33] Weber C. Novel mechanistic concepts for the control of leukocyte transmigration: specialization of integrins, chemokines, and junctional molecules. J Mol Med (Berl) 2003; 81(1): 4–19

[34] Jerke U, Rolle S, Purfürst B, Luft FC, Nauseef WM, Kettritz R. b2 integrin-mediated cell-cell contact transfers active myeloperoxidase from neutrophils to endothelial cells. J Biol Chem 2013; 288(18): 12910–12919

RIGHTS & PERMISSIONS

Higher Education Press and Springer-Verlag Berlin Heidelberg