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Lymphocyte subset characterization in patients with early clinical presentation of coronary heart disease

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Abstract

This study aimed to investigate lymphocyte populations in non-diabetic patients with early clinical presentation of coronary heart disease (CHD). Twenty-five consecutive middle-aged (<55 years) out-patients with CHD (acute myocardial infarction in the previous 3 months) and stable clinical conditions (>1 month) underwent venous blood sampling in order to determinate CD3+ (T-lymphocytes), CD19+ (B-lymphocytes), CD4+ (helper/inducer lymphocytes) and CD8+ (suppressor/cytotoxic lymphocytes) populations. Patients with diabetes, heart failure symptoms, recent revascularization (<30 days) were excluded. Twenty-five patients matched for age, gender and risk factors were enrolled as controls. All patients with CHD previously underwent coronary angiography. CHD patients showed lower CD3+ levels (70.96 ± 4.72 vs. 74.12 ± 4.93 %, p < 0.05) and CD8+ (37.80 ± 7.15 vs. 46.36 ± 5.22 %, p < 0.001) but higher CD4+ (37.32 ± 7.99 vs. 31.64 ± 4.72 %, p < 0.01) and CD4+/CD8+ ratio (1.06 ± 0.43 vs. 0.69 ± 0.13, p < 0.001). Difference in CD19+ levels was not statistically significant. Subjects with an impaired (≤55 %) left ventricular ejection fraction were characterized by lower levels of CD8+ (33.23 ± 7.04 vs. 43.76 ± 7.40 %, p < 0.05) and higher levels of CD4+ (38.31 ± 8.23 vs. 32.73 ± 6.08 %, p < 0.05) and CD4+/CD8+ ratio (1.06 ± 0.38 vs. 0.79 ± 0.34, p < 0.05). CD8+ levels inversely related to severity of coronary atherosclerosis (r = −0.37, p < 0.01). In conclusion, subjects with early clinical presentation of CHD are characterized by an altered CD4+/CD8+ ratio and lower CD3+ levels.

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References

  1. Grassi M, Assanelli D, Mozzini C, Albertini F, Salvadori G, Archetti S, Negrini R, Galeazzi G, Pezzini A (2005) Modeling premature occurrence of acute coronary syndrome with atherogenic and thrombogenic risk factors and gene markers in extended families. J Thromb Haemost 3:2238–2244

    Article  PubMed  CAS  Google Scholar 

  2. Caimi G, Hoffmann E, Montana M, Canino B, Dispensa F, Catania A, Lo Presti R (2003) Haemorheological pattern in young adults with acute myocardial infarction. Clin Hemorheol Microcirc 29(11–8):16

    Google Scholar 

  3. Pineda J, Marín F, Marco P, Roldán V, Valencia J, Ruiz-Nodar JM, Sogorb F, Lip GY (2009) Premature coronary artery disease in young (age < 45) subjects: interactions of lipid profile, thrombophilic and haemostatic markers. Int J Cardiol 136:222–225

    Article  PubMed  Google Scholar 

  4. Hansson GK, Jonasson L (2009) The discovery of cellular immunity in the atherosclerotic plaque. Arterioscler Thromb Vasc Biol 29:1714–1717

    Article  PubMed  CAS  Google Scholar 

  5. Robertson AKL, Hansson GK (2006) T cells in atherogenesis. For better or for worse? Arterioscler Thromb Vasc Biol 26:2421–2432

    Article  PubMed  CAS  Google Scholar 

  6. Libby P, Ridker PM, Hansson GK (2009) Inflammation in atherosclerosis. From pathophysiology to practice. J Am Coll Cardiol 54:2129–2138

    Article  PubMed  CAS  Google Scholar 

  7. Hansson GK (2001) Immune mechanisms in atherosclerosis. Arterioscler Thromb Vasc Biol 21:1876–1890

    Article  PubMed  CAS  Google Scholar 

  8. Toutouzas K, Drakopoulou M, Markou V, Karabelas I, Vaina S, Vavuranakis M, Tsiamis E, Tsioufis C, Androulakis A, Stefanadis C (2007) Correlation of systemic inflammation with local inflammatory activity in non-culprit lesions: beneficial effect of statins. Int J Cardiol 119:368–373

    Article  PubMed  Google Scholar 

  9. Fernandes JL, Mamoni RL, Orford JL, Garcia C, Selwyn AP, Coelho OR, Blotta MH (2004) Increased Th1 activity in patients with coronary artery disease. Cytokine 26:131–137

    Article  PubMed  CAS  Google Scholar 

  10. Steppich BA, Moog P, Matissek C, Wisniowski N, Kühle J, Joghetaei N, Neumann FJ, Schomig A, Ott I (2007) Cytokine profiles and T cell function in acute coronary syndromes. Atherosclerosis 190:443–451

    Article  PubMed  CAS  Google Scholar 

  11. van der Wal AC, Piek JJ, de Boer OJ, Koch KT, Teeling P, van der Loos CM, Becker AE (1998) Recent activation of the plaque immune response in coronary lesions underlying acute coronary syndromes. Heart 80:14–18

    PubMed  Google Scholar 

  12. Cheng X, Liao YH, Ge H, Li B, Zhang J, Yuan J, Wang M, Liu Y, Guo Z, Chen J, Zhang J, Zhang L (2005) TH1/TH2 functional imbalance after acute myocardial infarction: coronary arterial inflammation or myocardial inflammation. J Clin Immunol 25:246–253

    Article  PubMed  CAS  Google Scholar 

  13. Hosono M, de Boer OJ, van der Wal AC, van der Loos CM, Teeling P, Piek JJ, Ueda M, Becker AE (2003) Increased expression of T cell activation markers (CD25, CD26, CD40L and CD69) in atherectomy specimens of patients with unstable angina and acute myocardial infarction. Atherosclerosis 168:73–80

    Article  PubMed  CAS  Google Scholar 

  14. Mosmann TR, Sad S (1996) The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today 17:138–146

    Article  PubMed  CAS  Google Scholar 

  15. Zhou X (2003) CD4+ T cells in atherosclerosis. Biomed Pharmacother 57:287–291

    Article  PubMed  CAS  Google Scholar 

  16. Hansson GK (2009) Inflammatory mechanisms in atherosclerosis. J Thromb Haemost 7(Suppl 1):328–331

    Article  PubMed  CAS  Google Scholar 

  17. Zhao Z, Wu Y, Cheng M, Ji Y, Yang X, Liu P, Jia S, Yuan Z (2011) Activation of Th17/Th1 and Th1, but not Th17, is associated with the acute cardiac event in patients with acute coronary syndrome. Atherosclerosis 217(2):518–524

    Article  PubMed  CAS  Google Scholar 

  18. Davenport P, Tipping PG (2003) The role of interleukin-4 and interleukin-12 in the progression of atherosclerosis in apolipoprotein E-deficient mice. Am J Pathol 163:1117–1125

    Article  PubMed  CAS  Google Scholar 

  19. Brunetti ND, Pepe M, Munno I, Tiecco F, Quagliara D, De Gennaro L, Gaglione A, Di Biase M, Favale S (2008) Th2-dependent cytokine release in patients treated with coronary angioplasty. Coron Artery Dis 19:133–137

    Article  PubMed  Google Scholar 

  20. Ait-Oufella H, Salomon BL, Potteaux S, Robertson AK, Gourdy P, Zoll J, Merval R, Esposito B, Cohen JL, Fisson S, Flavell RA, Hansson GK, Klatzmann D, Tedgui A, Mallat Z (2006) Natural regulatory T cells control the development of atherosclerosis in mice. Nat Med 12:178–180

    Article  PubMed  CAS  Google Scholar 

  21. Ludewig B, Freigang S, Jaggi M, Kurrer MO, Pei YC, Vlk L, Odermatt B, Zinkernagel RM, Hengartner H (2000) Linking immune-mediated arterial inflammation and cholesterol-induced atherosclerosis in a transgenic mouse model. Proc Natl Acad Sci USA 97:12752–12757

    Article  PubMed  CAS  Google Scholar 

  22. Garlichs CD, Cicha I, Raaz D, Meyer L, Stumpf C, Klinghammer L, Yilmaz A, Daniel WG (2009) CD40/CD154 system and pro-inflammatory cytokines in young healthy male smokers without additional risk factors for atherosclerosis. Inflamm Res 58:306–311

    Article  PubMed  CAS  Google Scholar 

  23. Syrjälä H, Surcel HM, Ilonen J (1991) Low CD4/CD8 T lymphocyte ratio in acute myocardial infarction. Clin Exp Immunol 83:326–328

    Article  PubMed  Google Scholar 

  24. Blum A, Sclarovsky S, Rehavia E, Shohat B (1994) Levels of T-lymphocyte subpopulations, interleukin-1 beta, and soluble interleukin-2 receptor in acute myocardial infarction. Am Heart J 127:1226–1230

    Article  PubMed  CAS  Google Scholar 

  25. Frostegard J, Ulfgren AK, Nyberg P, Hedin U, Swedenborg J, Andersson U, Hansson GK (1999) Cytokine expression in advanced human atherosclerotic plaques: dominance of pro-inflammatory (Th1) and macrophage-stimulating cytokines. Atherosclerosis 145:33–43

    Article  PubMed  CAS  Google Scholar 

  26. Roselaar SE, Kakkanathu PX, Daugherty A (1996) Lymphocyte populations in atherosclerotic lesions of apoE−/− and LDL receptor−/− mice. Decreasing density with disease progression. Arterioscler Thromb Vasc Biol 16:1013–1018

    Article  PubMed  CAS  Google Scholar 

  27. Zhou X, Stemme S, Hansson GK (1996) Evidence for a local immune response in atherosclerosis: CD4+ T cells infiltrate lesions of apolipoprotein-E-deficient mice. Am J Pathol 149:359–366

    PubMed  CAS  Google Scholar 

  28. Zhou X, Nicoletti A, Elhage R, Hansson GK (2000) Transfer of CD4(+) T cells aggravates atherosclerosis in immunodeficient apolipoprotein E knockout mice. Circulation 102:2919–2922

    Article  PubMed  CAS  Google Scholar 

  29. Zhou X, Robertson AK, Hjerpe C, Hansson GK (2006) Adoptive transfer of CD4+ T cells reactive to modified low-density lipoprotein aggravates atherosclerosis. Arterioscler Thromb Vasc Biol 26(864–70):18

    Google Scholar 

  30. Pryshchep S, Sato K, Goronzy JJ, Weyand CM (2006) T cell recognition and killing of vascular smooth muscle cells in acute coronary syndrome. Circ Res 98:1168–1176

    Article  PubMed  CAS  Google Scholar 

  31. Alber HF, Frick M, Suessenbacher A, Doerler J, Schirmer M, Stocker EM, Dichtl W, Pachinger O, Weidinger F (2006) Effect of atorvastatin on circulating proinflammatory T-lymphocyte subsets and soluble CD40 ligand in patients with stable coronary artery disease—a randomized, placebo-controlled study. Am Heart J 151:139

    Article  PubMed  Google Scholar 

  32. Liuzzo G, Kopecky SL, Frye RL, O’Fallon WM, Maseri A, Goronzy JJ, Weyand CM (1999) Perturbation of the T-cell repertoire in patients with unstable angina. Circulation 100:2135–2139

    Article  PubMed  CAS  Google Scholar 

  33. Tanigawa T, Kitamura A, Yamagishi K, Sakurai S, Nakata A, Yamashita H, Sato S, Ohira T, Imano H, Shimamoto T, Iso H (2003) Relationships of differential leukocyte and lymphocyte subpopulations with carotid atherosclerosis in elderly men. J Clin Immunol 23:469–476

    Article  PubMed  Google Scholar 

  34. Gökçe M, Erdöl C, Örem C, Tekelioglu Y, Durmus I, Kasap H (2002) Inflammation and immune system response against unstable angina and its relationship with coronary angiographic findings. Jpn Heart J 43:593–605

    Article  PubMed  Google Scholar 

  35. Kolbus D, Ramos OH, Berg KE, Persson J, Wigren M, Björkbacka H, Fredrikson GN, Nilsson J (2010) CD8+ T cell activation predominate early immune responses to hypercholesterolemia in Apoe−(/)− mice. BMC Immunol 11:58

    Article  PubMed  CAS  Google Scholar 

  36. Gewaltig J, Kummer M, Koella C, Cathomas G, Biedermann BC (2008) Requirements for CD8 T-cell migration into the human arterial wall. Hum Pathol 39:1756–1762

    Article  PubMed  CAS  Google Scholar 

  37. Nadareishvili ZG, Koziol DE, Szekely B, Ruetzler C, LaBiche R, McCarron R, DeGraba TJ (2001) Increased CD8(+) T cells associated with Chlamydia pneumoniae in symptomatic carotid plaque. Stroke 32:1966–1972

    Article  PubMed  CAS  Google Scholar 

  38. Steffens S, Burger F, Pelli G, Dean Y, Elson G, Kosco-Vilbois M, Chatenoud L, Mach F (2006) Short-term treatment with anti-CD3 antibody reduces the development and progression of atherosclerosis in mice. Circulation 114:1977–1984

    Article  PubMed  CAS  Google Scholar 

  39. Smith JA, Tang Q, Bluestone JA (1998) Partial TCR signals delivered by FcR-nonbinding anti-CD3 monoclonal antibodies differentially regulate individual Th subsets. J Immunol 160:4841–4849

    PubMed  CAS  Google Scholar 

  40. Liu LL, Lu JL, Chao PL, Lin LR, Zhang ZY, Yang TC (2011) Lower prevalence of circulating invariant natural killer T (iNKT) cells in patients with acute myocardial infarction undergoing primary coronary stenting. Int Immunopharmacol 11:480–484

    Article  PubMed  CAS  Google Scholar 

  41. Emeson EE, Shen ML, Bell CG, Qureshi A (1996) Inhibition of atherosclerosis in CD4 T-cell-ablated and nude (nu/nu) C57BL/6 hyperlipidemic mice. Am J Pathol 149:675–685

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Cardiology Department, University of Foggia, Viale Pinto 1, 71100, Foggia, Italy

    Natale Daniele Brunetti, Carmine D’Antuono, Michele Rana, Girolamo D’Arienzo, Luisa De Gennaro & Matteo Di Biase

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  1. Natale Daniele Brunetti
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  2. Carmine D’Antuono
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  3. Michele Rana
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Correspondence to Natale Daniele Brunetti.

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Brunetti, N.D., D’Antuono, C., Rana, M. et al. Lymphocyte subset characterization in patients with early clinical presentation of coronary heart disease. J Thromb Thrombolysis 34, 475–482 (2012). https://doi.org/10.1007/s11239-012-0761-3

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