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A decrease in the percentage of circulating mDC precursors in patients with coronary heart disease: a relation to the severity and extent of coronary artery lesions?

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Abstract

Inflammation plays a pivotal role in coronary heart disease. Dendritic cells (DCs) are principal players in inflammation and atherosclerosis. Although the percentage of circulating DC precursors in coronary heart disease have been investigated, circulating myeloid DC (mDC) and plasmacytoid DC (pDC) precursors have not been extensively studied, particularly in relation to the severity of coronary artery lesions in patients with coronary heart disease. In this study, we recruited controls (n = 29), patients with stable angina pectoris (SAP, n = 30), patients with unstable angina pectoris (UAP, n = 56), and patients with acute myocardial infarction (AMI, n = 50). The severity and extent of coronary artery lesions was evaluated by Gensini score, following coronary angiograms. The percentage of circulating mDC and pDC precursors was determined by fluorescence-activated cell sorting (FACS). Plasma levels of MCP-1 and MMP-9, which correlate with atherosclerosis and DC migration, were also measured. The percentage of circulating mDC precursors was reduced in patients with AMI and UAP compared with control and SAP patients, respectively (p < 0.01 for AMI vs. SAP and Control, p < 0.05 for UAP vs. SAP and Control). The percentage of circulating pDC precursors was not significant changed. The levels of plasma MMP-9 and MCP-1 and Genisi score were all increased in patients with AMI and UAP, compared to control and SAP patients, respectively (p < 0.01 for AMI vs. SAP and control, p < 0.05 for UAP vs. SAP and control). Overall, the percentage of circulating mDC precursors was negatively correlated with MCP-1 (p < 0.001), MMP-9 (p < 0.001) and Genisi scores (p < 0.001). Genisi scores were positively correlated with the levels of MCP-1 (p < 0.001) and MMP-9 (p < 0.001). Our study suggested that the percentage of circulating mDC precursors is negatively correlated with the severity and extent of coronary artery lesions in patients with coronary heart disease.

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References

  1. Mirzaei M, Truswell AS, Taylor R, Leeder SR (2009) Coronary heart disease epidemics: not all the same. Heart 95:740–746

    Article  PubMed  CAS  Google Scholar 

  2. Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352:1685–1695

    Article  PubMed  CAS  Google Scholar 

  3. Galkina E, Ley K (2009) Immune and inflammatory mechanisms of atherosclerosis (*). Annu Rev Immunol 27:165–197

    Article  PubMed  CAS  Google Scholar 

  4. Bobryshev YV (2010) Dendritic cells and their role in atherogenesis. Lab Invest 90:970–984

    Article  PubMed  Google Scholar 

  5. Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B, Palucka K (2000) Immunobiology of dendritic cells. Annu Rev Immunol 18:767–811

    Article  PubMed  CAS  Google Scholar 

  6. Robinson SP, Patterson S, English N, Davies D, Knight SC, Reid CD (1999) Human peripheral blood contains two distinct lineages of dendritic cells. Eur J Immunol 29:2769–2778

    Article  PubMed  CAS  Google Scholar 

  7. Niessner A, Weyand CM (2010) Dendritic cells in atherosclerotic disease. Clin Immunol 134:25–32

    Article  PubMed  CAS  Google Scholar 

  8. Bobryshev YV, Lord RS (1995) Ultrastructural recognition of cells with dendritic cell morphology in human aortic intima. Contacting interactions of vascular dendritic cells in athero-resistant and athero-prone areas of the normal aorta. Arch Histol Cytol 58:307–322

    Article  PubMed  CAS  Google Scholar 

  9. Paulson KE, Zhu SN, Chen M, Nurmohamed S, Jongstra-Bilen J, Cybulsky MI (2010) Resident intimal dendritic cells accumulate lipid and contribute to the initiation of atherosclerosis. Circ Res 106:383–390

    Article  PubMed  CAS  Google Scholar 

  10. Jongstra-Bilen J, Haidari M, Zhu SN, Chen M, Guha D, Cybulsky MI (2006) Low-grade chronic inflammation in regions of the normal mouse arterial intima predisposed to atherosclerosis. J Exp Med 203:2073–2083

    Article  PubMed  CAS  Google Scholar 

  11. Liu P, Yu YR, Spencer JA, Johnson AE, Vallanat CT, Fong AM, Patterson C, Patel DD (2008) CX3CR1 deficiency impairs dendritic cell accumulation in arterial intima and reduces atherosclerotic burden. Arterioscler Thromb Vasc Biol 28:243–250

    Article  PubMed  CAS  Google Scholar 

  12. Yilmaz A, Lochno M, Traeg F, Cicha I, Reiss C, Stumpf C, Raaz D, Anger T, Amann K, Probst T, Ludwig J, Daniel WG, Garlichs CD (2004) Emergence of dendritic cells in rupture-prone regions of vulnerable carotid plaques. Atherosclerosis 176:101–110

    Article  PubMed  CAS  Google Scholar 

  13. Bobryshev YV, Lord RS (2005) Co-accumulation of dendritic cells and natural killer T cells within rupture-prone regions in human atherosclerotic plaques. J Histochem Cytochem 53:781–785

    Article  PubMed  CAS  Google Scholar 

  14. Kawahara I, Kitagawa N, Tsutsumi K, Nagata I, Hayashi T, Koji T (2007) The expression of vascular dendritic cells in human atherosclerotic carotid plaques. Hum Pathol 38:1378–1385

    Article  PubMed  CAS  Google Scholar 

  15. Yilmaz A, Weber J, Cicha I, Stumpf C, Klein M, Raithel D, Daniel WG, Garlichs CD (2006) Decrease in circulating myeloid dendritic cell precursors in coronary artery disease. J Am Coll Cardiol 48:70–80

    Article  PubMed  CAS  Google Scholar 

  16. Fu Q, Li ZL, Lei X, Fu XH, Yan QN, Liu YF (2008) Peripheral dendritic cell subpopulation changes in patients with coronary artery disease. Zhonghua Xin Xue Guan Bing Za Zhi 36:209–211

    PubMed  CAS  Google Scholar 

  17. Yilmaz A, Reiss C, Weng A, Cicha I, Stumpf C, Steinkasserer A, Daniel WG, Garlichs CD (2006) Differential effects of statins on relevant functions of human monocyte-derived dendritic cells. J Leukoc Biol 79:529–538

    Article  PubMed  CAS  Google Scholar 

  18. Tu Y, Jia R, Ding G, Chen L (2010) Effect of atorvastatin on dendritic cells of tubulointerstitium in diabetic rats. BMB Rep 43:188–192

    Article  PubMed  CAS  Google Scholar 

  19. Niessner A, Sato K, Chaikof EL, Colmegna I, Goronzy JJ, Weyand CM (2006) Pathogen-sensing plasmacytoid dendritic cells stimulate cytotoxic T-cell function in the atherosclerotic plaque through interferon-alpha. Circulation 114(23):2482–2489

    Article  PubMed  CAS  Google Scholar 

  20. Niessner A, Shin MS, Pryshchep O, Goronzy JJ, Chaikof EL, Weyand CM (2007) Synergistic proinflammatory effects of the antiviral cytokine interferon-alpha and Toll-like receptor 4 ligands in the atherosclerotic plaque. Circulation 116(18):2043–2052

    Article  PubMed  CAS  Google Scholar 

  21. Yilmaz A, Lipfert B, Cicha I, Schubert K, Klein M, Raithel D, Daniel WG, Garlichs CD (2007) Accumulation of immune cells and high expression of chemokines/chemokine receptors in the upstream shoulder of atherosclerotic carotid plaques. Exp Mol Pathol 82:245–255

    Article  PubMed  CAS  Google Scholar 

  22. Xu ZX, Yang YZ, Feng DM, Wang S, Tang YL, He F, Xia Y, Li F (2008) Oxidized high-density lipoprotein promotes maturation and migration of bone marrow derived dendritic cells from C57BL/6J mice. Chin Med Sci J 23:224–229

    Article  PubMed  Google Scholar 

  23. Dong K, Ge JH, Gu SL, Li S, Zhu WG, Fan FY, Zhu JH (2011) Ox-LDL can enhance the interaction of mice natural killer cells and dendritic cells via the CD48-2B4 pathway. Heart Vessels. doi:10.1007/s00380-010-0102-4

  24. Gu L, Okada Y, Clinton SK, Gerard C, Sukhova GK, Libby P, Rollins BJ (1998) Absence of monocyte chemoattractant protein-1 reduces atherosclerosis in low-density lipoprotein receptor-deficient mice. Mol Cell 2:275–281

    Article  PubMed  CAS  Google Scholar 

  25. Inoue S, Egashira K, Ni W, Kitamoto S, Usui M, Otani K, Ishibashi M, Hiasa K, Nishida K, Takeshita A (2002) Anti-monocyte chemoattractant protein-1 gene therapy limits progression and destabilization of established atherosclerosis in apolipoprotein E-knockout mice. Circulation 106:2700–2706

    Article  PubMed  CAS  Google Scholar 

  26. Boring L, Gosling J, Cleary M, Charo IF (1998) Decreased lesion formation in CCR2−/− mice reveals a role for chemokines in the initiation of atherosclerosis. Nature 394:894–897

    Article  PubMed  CAS  Google Scholar 

  27. Ni W, Kitamoto S, Ishibashi M, Usui M, Inoue S, Hiasa K, Zhao Q, Nishida K, Takeshita A, Egashira K (2004) Monocyte chemoattractant protein-1 is an essential inflammatory mediator in angiotensin II-induced progression of established atherosclerosis in hypercholesterolemic mice. Arterioscler Thromb Vasc Biol 24:534–539

    Article  PubMed  CAS  Google Scholar 

  28. de Lemos JA, Morrow DA, Sabatine MS, Murphy SA, Gibson CM, Antman EM, McCabe CH, Cannon CP, Braunwald E (2003) Association between plasma levels of monocyte chemoattractant protein-1 and long-term clinical outcomes in patients with acute coronary syndromes. Circulation 107:690–695

    Article  PubMed  Google Scholar 

  29. de Lemos JA, Morrow DA, Blazing MA, Jarolim P, Wiviott SD, Sabatine MS, Califf RM, Braunwald E (2007) Serial measurement of monocyte chemoattractant protein-1 after acute coronary syndromes: results from the A to Z trial. J Am Coll Cardiol 50:2117–2124

    Article  PubMed  Google Scholar 

  30. Gonzalez-Quesada C, Frangogiannis NG (2009) Monocyte chemoattractant protein-1/CCL2 as a biomarker in acute coronary syndromes. Curr Atheroscler Rep 11:131–138

    Article  PubMed  CAS  Google Scholar 

  31. Jimenez F, Quinones MP, Martinez HG, Estrada CA, Clark K, Garavito E, Ibarra J, Melby PC, Ahuja SS (2010) CCR2 plays a critical role in dendritic cell maturation: possible role of CCL2 and NF-kappa B. J Immunol 184:5571–5581

    Article  PubMed  CAS  Google Scholar 

  32. Hu Y, Ivashkiv LB (2006) Costimulation of chemokine receptor signaling by matrix metalloproteinase-9 mediates enhanced migration of IFN-alpha dendritic cells. J Immunol 176:6022–6033

    PubMed  CAS  Google Scholar 

  33. Yen JH, Khayrullina T, Ganea D (2008) PGE2-induced metalloproteinase-9 is essential for dendritic cell migration. Blood 111:260–270

    Article  PubMed  CAS  Google Scholar 

  34. Ionita MG, Vink A, Dijke IE, Laman JD, Peeters W, van der Kraak PH, Moll FL, de Vries JP, Pasterkamp G, de Kleijn DP (2009) High levels of myeloid-related protein 14 in human atherosclerotic plaques correlate with the characteristics of rupture-prone lesions. Arterioscler Thromb Vasc Biol 29:1220–1227

    Article  PubMed  CAS  Google Scholar 

  35. Chen HQ, Tan HY, Yang YW, Qiu L, Liu XQ (2010) Effects of ramipril on serum monocyte chemoattractant protein 1, interleukin-18, and interleukin-10 in elderly patients with acute coronary syndrome. Heart Vessels 25(2):77–81

    Article  PubMed  CAS  Google Scholar 

  36. Yokota T, Osanai T, Hanada K, Kushibiki M, Abe N, Oikawa K, Tomita H, Higuma T, Yokoyama J, Hanada H, Okumura K (2010) Effects of telmisartan on markers of ventricular remodeling in patients with acute myocardial infarction: comparison with enalapril. Heart Vessels 25(6):460–468

    Article  PubMed  Google Scholar 

  37. Fukunaga T, Soejima H, Irie A, Fukushima R, Oe Y, Kawano H, Sumida H, Kaikita K, Sugiyama S, Nishimura Y, Ogawa H (2009) High ratio of myeloid dendritic cells to plasmacytoid dendritic cells in blood of patients with acute coronary syndrome. Circ J 73:1914–1919

    Article  PubMed  Google Scholar 

  38. Erbel C, Sato K, Meyer FB, Kopecky SL, Frye RL, Goronzy JJ, Weyand CM (2007) Functional profile of activated dendritic cells in unstable atherosclerotic plaque. Basic Res Cardiol 102:123–132

    Article  PubMed  CAS  Google Scholar 

  39. Angeli V, Llodra J, Rong JX, Satoh K, Ishii S, Shimizu T, Fisher EA, Randolph GJ (2004) Dyslipidemia associated with atherosclerotic disease systemically alters dendritic cell mobilization. Immunity 21:561–574

    Article  PubMed  CAS  Google Scholar 

  40. Smith SJ, Zheng ZJ (2010) The impending cardiovascular pandemic in China. Circ Cardiovasc Qual Outcomes 3:226–227

    Article  PubMed  Google Scholar 

  41. Zaguri R, Verbovetski I, Atallah M, Trahtemberg U, Krispin A, Nahari E, Leitersdorf E, Mevorach D (2007) ‘Danger’ effect of low-density lipoprotein (LDL) and oxidized LDL on human immature dendritic cells. Clin Exp Immunol 149:543–552

    Article  PubMed  CAS  Google Scholar 

  42. Blank SE, Johnson EC, Weeks DK, Wysham CH (2010) Circulating dendritic cell number and intracellular TNF-alpha production in women with type 2 diabetes. Acta Diabetol. doi:10.1007/s00592-010-0190-8

  43. Zeyda M, Kirsch BM, Geyeregger R, Stuhlmeier KM, Zlabinger GJ, Horl WH, Saemann MD, Stulnig TM (2005) Inhibition of human dendritic cell maturation and function by the novel immunosuppressant FK778. Transplantation 80:1105–1111

    Article  PubMed  CAS  Google Scholar 

  44. Lapteva N, Ide K, Nieda M, Ando Y, Hatta-Ohashi Y, Minami M, Dymshits G, Egawa K, Juji T, Tokunaga K (2002) Activation and suppression of renin-angiotensin system in human dendritic cells. Biochem Biophys Res Commun 296:194–200

    Article  PubMed  CAS  Google Scholar 

  45. Zhao P, Li XG, Yang M, Shao Q, Wang D, Liu S, Song H, Song B, Zhang Y, Qu X (2008) Hypoxia suppresses the production of MMP-9 by human monocyte-derived dendritic cells and requires activation of adenosine receptor A2b via cAMP/PKA signaling pathway. Mol Immunol 45:2187–2195

    Article  PubMed  CAS  Google Scholar 

  46. Ardans JA, Economou AP, Martinson JJ, Zhou M, Wahl LM (2002) Oxidized low-density and high-density lipoproteins regulate the production of matrix metalloproteinase-1 and -9 by activated monocytes. J Leukoc Biol 71:1012–1018

    PubMed  CAS  Google Scholar 

  47. Nurkic J, Ljuca F, Nurkic M, Jahic E, Jahic M (2010) Biomarkers of plaque instability in acute coronary syndrome patients. Med Arh 64:103–106

    PubMed  Google Scholar 

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Acknowledgments

This study was support by Grant number 2009B030801206 from 2009 Guangdong technology project.

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Correspondence to Fu Qiang.

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Wen, J., Wen, Y., Zhiliang, L. et al. A decrease in the percentage of circulating mDC precursors in patients with coronary heart disease: a relation to the severity and extent of coronary artery lesions?. Heart Vessels 28, 135–142 (2013). https://doi.org/10.1007/s00380-011-0218-1

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