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Monocyte subsets and monocyte-platelet aggregates in patients with unstable angina

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Abstract

Monocyte subsets and monocyte-platelet aggregates (MPAs) play important role in atherosclerosis and thrombosis. We aimed to determine their changes in patients with unstable angina (UA). In this cross-sectional case–control study, Global Registry of Acute Coronary Events (GRACE) score was determined in 95 UA patients without elevated troponin level. Thirty age-and-sex matched stable coronary heart disease (CHD) subjects served as control group. The classical (CD14++CD16−, Mon1), the intermediate (CD14++CD16+, Mon2) and the non-classical (CD14+CD16++, Mon3) monocytes, as well as subset-specific MPAs, were measured by flow cytometry. Compared with stable CHD patients, UA patients had increased Mon2 and Mon3 counts (all P < 0.001). For UA subjects, compared with GRACE score-determined low risk patients (GRACE score ≤108, n = 70), intermediate-to-high risk patients (GRACE score >108, n = 25) had higher counts of Mon2 and total MPAs, as well as Mon1- and Mon2-associated MPAs (all P < 0.001). Adjusted binary logistic regression analysis revealed that increased counts of Mon2 subset (for per 5 cells/μL increase, OR 1.186, 95 % CI 1.044–1.347, P = 0.009), Mon2 MPAs (for per 5 cells/μL increase, OR 1.228, 95 % CI 1.062–1.421, P = 0.006) and total MPAs (for per 5 cells/μL increase, OR 1.072, 95 % CI 1.010–1.137, P = 0.022) independently associated with GRACE score-determined intermediate-to-high risk UA patients. In UA patients with intermediate-to-high risk (determined by GRACE score), counts of Mon2 subset, Mon2-associated MPAs and total MPAs are increased, which are independent of traditional risk factors.

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References

  1. Giugliano RP, Braunwald E (2012) The year in non-ST-segment elevation acute coronary syndrome. J Am Coll Cardiol 60:2127–2139. doi:10.1016/2012.08.972

    Article  PubMed  Google Scholar 

  2. Weber M, Bazzino O, Navarro-Estrada JL, Fuselli JJ, Botto F, de Perez-Arenaza D et al (2008) N-terminal B-type natriuretic peptide assessment provides incremental prognostic information in patients with acute coronary syndromes and normal troponin T values upon admission. J Am Coll Cardiol 51:1188–1195. doi:10.1016/2007.11.054

    Article  PubMed  CAS  Google Scholar 

  3. Lindahl B, Toss H, Siegbahn A, Venge P, Wallentin L (2000) Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. FRISC Study Group. Fragmin during instability in coronary artery disease. N Engl J Med 343:1139–1147. doi:10.1056/200010193431602

    Article  PubMed  CAS  Google Scholar 

  4. Swirski FK, Nahrendorf M (2013) Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure. Science 339:161–166. doi:10.1126/1230719

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  5. Ghattas A, Griffiths HR, Devitt A, Lip GY, Shantsila E (2013) Monocytes in coronary artery disease and atherosclerosis: where are we now? J Am Coll Cardiol 62:1541–1551. doi:10.1016/2013.07.043

    Article  PubMed  CAS  Google Scholar 

  6. Dutta P, Courties G, Wei Y, Leuschner F, Gorbatov R, Robbins CS et al (2012) Myocardial infarction accelerates atherosclerosis. Nature 487:325–329. doi:10.1038/11260

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  7. Jaipersad AS, Lip GY, Silverman S, Shantsila E (2014) The role of monocytes in angiogenesis and atherosclerosis. J Am Coll Cardiol 63:1–11. doi:10.1016/2013.09.019

    Article  PubMed  CAS  Google Scholar 

  8. Woollard KJ, Geissmann F (2010) Monocytes in atherosclerosis: subsets and functions. Nat Rev Cardiol 7:77–86. doi:10.1038/2009.228

    Article  PubMed  PubMed Central  Google Scholar 

  9. Ziegler-Heitbrock L, Ancuta P, Crowe S, Dalod M, Grau V, Hart DN et al (2010) Nomenclature of monocytes and dendritic cells in blood. Blood 116:e74–e80. doi:10.1182/2010-02-258558

    Article  PubMed  CAS  Google Scholar 

  10. Shantsila E, Lip GY (2009) Monocytes in acute coronary syndromes. Arterioscler Thromb Vasc Biol 29:1433–1438. doi:10.1161/108.180513

    Article  PubMed  CAS  Google Scholar 

  11. Shantsila E, Lip GY (2009) The role of monocytes in thrombotic disorders. Insights from tissue factor, monocyte-platelet aggregates and novel mechanisms. Thromb Haemost 102:916–924. doi:10.1160/09-01-0023

    PubMed  CAS  Google Scholar 

  12. Furman MI, Barnard MR, Krueger LA, Fox ML, Shilale EA, Lessard DM et al (2001) Circulating monocyte-platelet aggregates are an early marker of acute myocardial infarction. J Am Coll Cardiol 38:1002–1006

    Article  PubMed  CAS  Google Scholar 

  13. Michelson AD, Barnard MR, Krueger LA, Valeri CR, Furman MI (2001) Circulating monocyte-platelet aggregates are a more sensitive marker of in vivo platelet activation than platelet surface P-selectin: studies in baboons, human coronary intervention, and human acute myocardial infarction. Circulation 104:1533–1537

    Article  PubMed  CAS  Google Scholar 

  14. Eagle KA, Lim MJ, Dabbous OH, Pieper KS, Goldberg RJ, Van de Werf F et al (2004) A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month postdischarge death in an international registry. JAMA 291:2727–2733. doi:10.1001/291.22.2727

    Article  PubMed  CAS  Google Scholar 

  15. Fox KA, Dabbous OH, Goldberg RJ, Pieper KS, Eagle KA, Van de Werf F et al (2006) Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE). BMJ 333:1091. doi:10.1136/38985.646481.55

    Article  PubMed  PubMed Central  Google Scholar 

  16. Granger CB, Goldberg RJ, Dabbous O, Pieper KS, Eagle KA, Cannon CP et al (2003) Predictors of hospital mortality in the global registry of acute coronary events. Arch Intern Med 163:2345–2353. doi:10.1001/163.19.2345

    Article  PubMed  Google Scholar 

  17. Apple FS (2009) A new season for cardiac troponin assays: it’s time to keep a scorecard. Clin Chem 55:1303–1306. doi:10.1373/2009.128363

    Article  PubMed  CAS  Google Scholar 

  18. Zhou X, Zhang L, Ji WJ, Yuan F, Guo ZZ, Pang B et al (2013) Variation in dietary salt intake induces coordinated dynamics of monocyte subsets and monocyte-platelet aggregates in humans: implications in end organ inflammation. PLoS ONE 8:e60332. doi:10.1371/0060332

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  19. Shantsila E, Tapp LD, Wrigley BJ, Montoro-Garcia S, Ghattas A, Jaipersad A et al (2012) The effects of exercise and diurnal variation on monocyte subsets and monocyte-platelet aggregates. Eur J Clin Invest 42:832–839. doi:10.1111/1365-2362.2012.02656.x

    Article  PubMed  CAS  Google Scholar 

  20. Sianos G, Morel MA, Kappetein AP, Morice MC, Colombo A, Dawkins K et al (2005) The SYNTAX Score: an angiographic tool grading the complexity of coronary artery disease. EuroIntervention 1:219–227

    PubMed  Google Scholar 

  21. Hamm CW, Bassand JP, Agewall S, Bax J, Boersma E, Bueno H et al (2011) ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: the Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 32:2999–3054. doi:10.1093/236

    Article  PubMed  Google Scholar 

  22. Viswanathan K, Kilcullen N, Morrell C, Thistlethwaite SJ, Sivananthan MU, Hassan TB et al (2010) Heart-type fatty acid-binding protein predicts long-term mortality and re-infarction in consecutive patients with suspected acute coronary syndrome who are troponin-negative. J Am Coll Cardiol 55:2590–2598. doi:10.1016/2009.12.062

    Article  PubMed  CAS  Google Scholar 

  23. Rogacev KS, Ulrich C, Blomer L, Hornof F, Oster K, Ziegelin M et al (2010) Monocyte heterogeneity in obesity and subclinical atherosclerosis. Eur Heart J 31:369–376. doi:10.1093/308

    Article  PubMed  CAS  Google Scholar 

  24. Rogacev KS, Seiler S, Zawada AM, Reichart B, Herath E, Roth D et al (2011) CD14++CD16+ monocytes and cardiovascular outcome in patients with chronic kidney disease. Eur Heart J 32:84–92. doi:10.1093/371

    Article  PubMed  CAS  Google Scholar 

  25. Kashiwagi M, Imanishi T, Tsujioka H, Ikejima H, Kuroi A, Ozaki Y et al (2010) Association of monocyte subsets with vulnerability characteristics of coronary plaques as assessed by 64-slice multidetector computed tomography in patients with stable angina pectoris. Atherosclerosis 212:171–176. doi:10.1016/2010.05.004

    Article  PubMed  CAS  Google Scholar 

  26. Majmudar MD, Keliher EJ, Heidt T, Leuschner F, Truelove J, Sena BF et al (2013) Monocyte-directed RNAi targeting CCR2 improves infarct healing in atherosclerosis-prone mice. Circulation 127:2038–2046. doi:10.1161/112.000116

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  27. Zhou X, Luo YC, Ji WJ, Zhang L, Dong Y, Ge L et al (2013) Modulation of mononuclear phagocyte inflammatory response by liposome-encapsulated voltage gated sodium channel inhibitor ameliorates myocardial ischemia/reperfusion injury in rats. PLoS ONE 8:e74390. doi:10.1371/0074390

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  28. Zawada AM, Rogacev KS, Rotter B, Winter P, Marell RR, Fliser D et al (2011) SuperSAGE evidence for CD14++CD16+ monocytes as a third monocyte subset. Blood 118:e50–e61. doi:10.1182/2011-01-326827

    Article  PubMed  CAS  Google Scholar 

  29. Wong KL, Tai JJ, Wong WC, Han H, Sem X, Yeap WH et al (2011) Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets. Blood 118:e16–e31. doi:10.1182/2010-12-326355

    Article  PubMed  CAS  Google Scholar 

  30. Cros J, Cagnard N, Woollard K, Patey N, Zhang SY, Senechal B et al (2010) Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors. Immunity 33:375–386. doi:10.1016/2010.08.012

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  31. Imanishi T, Ikejima H, Tsujioka H, Kuroi A, Ishibashi K, Komukai K et al (2010) Association of monocyte subset counts with coronary fibrous cap thickness in patients with unstable angina pectoris. Atherosclerosis 212:628–635. doi:10.1016/2010.06.025

    Article  PubMed  CAS  Google Scholar 

  32. Schlitt A, Heine GH, Blankenberg S, Espinola-Klein C, Dopheide JF, Bickel C et al (2004) CD14+CD16+ monocytes in coronary artery disease and their relationship to serum TNF-alpha levels. Thromb Haemost 92:419–424. doi:10.1267/04080419

    PubMed  CAS  Google Scholar 

  33. Sarma J, Laan CA, Alam S, Jha A, Fox KA, Dransfield I (2002) Increased platelet binding to circulating monocytes in acute coronary syndromes. Circulation 105:2166–2171

    Article  PubMed  Google Scholar 

  34. Tapp LD, Shantsila E, Wrigley BJ, Pamukcu B, Lip GY (2012) The CD14++CD16+ monocyte subset and monocyte-platelet interactions in patients with ST-elevation myocardial infarction. J Thromb Haemost 10:1231–1241. doi:10.1111/1538-7836.2011.04603.x

    Article  PubMed  CAS  Google Scholar 

  35. Lukasik M, Dworacki G, Kufel-Grabowska J, Watala C, Kozubski W (2012) Upregulation of CD40 ligand and enhanced monocyte-platelet aggregate formation are associated with worse clinical outcome after ischaemic stroke. Thromb Haemost 107:346–355. doi:10.1160/11-05-0345

    Article  PubMed  CAS  Google Scholar 

  36. Wrigley BJ, Shantsila E, Tapp LD, Lip GY (2013) Increased formation of monocyte-platelet aggregates in ischemic heart failure. Circ Heart Fail 6:127–135

    Article  PubMed  CAS  Google Scholar 

  37. Rogacev KS, Cremers B, Zawada AM, Seiler S, Binder N, Ege P et al (2012) CD14++CD16+ monocytes independently predict cardiovascular events: a cohort study of 951 patients referred for elective coronary angiography. J Am Coll Cardiol 60:1512–1520. doi:10.1016/2012.07.019

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  39. Reichlin T, Twerenbold R, Maushart C, Reiter M, Moehring B, Schaub N et al (2013) Risk stratification in patients with unstable angina using absolute serial changes of 3 high-sensitive troponin assays. Am Heart J 165(371–378):e373. doi:10.1016/2012.11.010

    Google Scholar 

  40. Krueger LA, Barnard MR, Frelinger AL, 3rd, Furman MI, Michelson AD (2002) Immunophenotypic analysis of platelets. Curr Protoc Cytom Chapter 6:Unit 6–10. doi:10.1002/0471142956.cy0610s19

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (81170238, 81070121 and 81102088), Tianjin Municipal Science and Technology Committee (09ZCZDSF04200, 11JCYBJC12000 and 12JCYBJC16600) and intra-mural research grants from Pingjin Hospital (FYM201101 and FYM201104).

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Authors and Affiliations

  1. Graduate School of Medicine, Tianjin Medical University, Tianjin, China

    Shan Zeng

  2. Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Institute of Cardiovascular Disease and Heart Center, Pingjin Hospital, Logistics University of the Chinese People’s Armed Police Forces, 220, Cheng-Lin Road, Tianjin, China

    Shan Zeng, Xin Zhou, Lan Ge, Wen-Jie Ji, Rui Shi, Rui-Yi Lu, Hai-Ying Sun, Zhao-Zeng Guo, Ji-Hong Zhao, Tie-Min Jiang & Yu-Ming Li

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  1. Shan Zeng
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Correspondence to Yu-Ming Li.

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Shan Zeng and Xin Zhou authors have contributed equally to this work.

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Zeng, S., Zhou, X., Ge, L. et al. Monocyte subsets and monocyte-platelet aggregates in patients with unstable angina. J Thromb Thrombolysis 38, 439–446 (2014). https://doi.org/10.1007/s11239-014-1083-4

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