Heart and Vessels

, Volume 25, Issue 2, pp 77–81 | Cite as

Effects of ramipril on serum monocyte chemoattractant protein 1, interleukin-18, and interleukin-10 in elderly patients with acute coronary syndrome

  • Huan-qin Chen
  • Hong-yong Tan
  • Yi-wen Yang
  • Lei Qiu
  • Xiang-qun LiuEmail author
Original Article


Acute coronary syndrome (ACS) is a clinical syndrome caused by acute myocardial ischemia and a severe stage of coronary atherosclerosis heart disease. The aim of this study was to clarify whether ramipril was a therapeutic agent against monocyte chemoattractant protein 1 (MCP-1), interleukin 18 (IL-18), and interleukin 10 (IL-10) in elderly patients with ACS. A total of 190 subjects including 72 elderly patients with ACS (78.1% male, mean age 67.12 ± 5.06 years), 60 elderly patients with stable angina pectoris (76.9% male, mean age 68.00 ± 4.52 years), and 58 healthy volunteers (77.8% male, mean age 65.96 ± 4.18 years) were recruited into the study. Serum MCP-1, IL-10, and IL-18 were determined in 132 elderly patients by enzyme-linked immunosorbent assay (ELISA) before and after treatment with low doses of ramipril (2.5–5 mg/day), and were determined in 58 healthy volunteers. The levels of serum MCP-1 and IL-18 were much higher in elderly patients with ACS than those in elderly patients with SAP and healthy volunteers. After treating with ramipril, the levels of MCP-1 and IL-18 were decreased in elderly patients with ACS. Moreover, ramipril significantly increased serum IL-10 in elderly patients with ACS. Ramipril plays an important role in elderly patients with ACS. With decreasing MCP-1 and IL-18, it can ameliorate cytokine-associated cardiac damage. This study may provide a new recognition of angiotensinconverting enzyme inhibitor for the treatment of ACS.

Key words

Acute coronary syndrome Ramipril Monocyte chemoattractant protein 1 Interleukin-10 Interleukin-18 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ross R (1999) Atherosclerosis — an inflammatory disease. N Engl J Med 340(2):115–126CrossRefPubMedGoogle Scholar
  2. 2.
    Kinlay S, Schwartz GG, Olsson AG, Rifai N, Szarek M, Waters DD, Libby P, Ganz P; Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators (2008) Inflammation, statin therapy, and risk of stroke after an acute coronary syndrome in the MIRACL study. Arterioscler Thromb Vasc Biol 28(1):142–147CrossRefPubMedGoogle Scholar
  3. 3.
    Libby P (2001) Current concepts of the pathogenesis of the acute coronary syndromes. Circulation 104(3):365–372PubMedGoogle Scholar
  4. 4.
    Wang J, Zhang S, Jin Y, Qin G, Yu L, Zhang J (2007) Elevated levels of platelet-monocyte aggregates and related circulating biomarkers in patients with acute coronary syndrome. Int J Cardiol 115(3):361–365CrossRefPubMedGoogle Scholar
  5. 5.
    Yamaoka-Tojo M, Tojo T, Masuda T, Machida Y, Kitano Y, Kurosawa T, Izumi T (2003) C-reactive protein-induced production of interleukin-18 in human endothelial cells: a mechanism of orchestrating cytokine cascade in acute coronary syndrome. Heart Vessels 18(4):183–187CrossRefPubMedGoogle Scholar
  6. 6.
    Chalikias GK, Tziakas DN, Kaski JC, Hatzinikolaou EI, Stakos DA, Tentes IK, Kortsaris A, Hatseras DI (2005) Interleukin-18: interleukin-10 ratio and in-hospital adverse events in patients with acute coronary syndrome. Atherosclerosis 182(1):135–143CrossRefPubMedGoogle Scholar
  7. 7.
    Pasqui AL, Di Renzo M, Auteri A, Puccetti L (2005) Cytokines in acute coronary syndromes. Int J Cardiol 105(3):355–356CrossRefPubMedGoogle Scholar
  8. 8.
    Chalikias GK, Tziakas DN, Kaski JC, Kekes A, Hatzinikolaou EI, Stakos DA, Tentes IK, Kortsaris AX, Hatseras DI (2007) Interleukin-18/interleukin-10 ratio is an independent predictor of recurrent coronary events during a 1-year follow-up in patients with acute coronary syndrome. Int J Cardiol 117(3):333–339CrossRefPubMedGoogle Scholar
  9. 9.
    Soehnlein O, Schmeisser A, Cicha I, Reiss C, Ulbrich H, Lindbom L, Daniel WG, Garlichs CD (2005) ACE inhibition lowers angiotensin-II-induced monocyte adhesion to HUVEC by reduction of p65 translocation and AT 1 expression. J Vasc Res 42(5):399–407CrossRefPubMedGoogle Scholar
  10. 10.
    Lonn E, Yusuf S, Dzavik V, Doris C, Yi Q, Smith S, Moore-Cox A, Bosch J, Riley W, Teo K; SECURE Investigators (2001) Effects of ramipril and vitamin E on atherosclerosis: the Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and vitamin E (SECURE). Circulation 103(7):919–925PubMedGoogle Scholar
  11. 11.
    Oka H, Ikeda S, Koga S, Miyahara Y, Kohno S (2008) Atorvastatin induces associated reductions in platelet P-selectin, oxidized lowdensity lipoprotein, and interleukin-6 in patients with coronary artery diseases. Heart Vessels 23(4):249–256CrossRefPubMedGoogle Scholar
  12. 12.
    Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE (1992) Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 340(8828):1111–1115CrossRefPubMedGoogle Scholar
  13. 13.
    Gnasso A, Irace C, Carallo C, De Franceschi MS, Motti C, Mattioli PL, Pujia A (1997) In vivo association between low shear stress and plaque in subjects with asymmetrical carotid atherosclerosis. Stroke 28(5):993–998PubMedGoogle Scholar
  14. 14.
    van der Wal AC, Becker AE (1999) Atherosclerotic plaque rupture-pathologic basis of plaque stability and instability. Cardiovasc Res 41(2):334–344CrossRefPubMedGoogle Scholar
  15. 15.
    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(5):690–695CrossRefPubMedGoogle Scholar
  16. 16.
    Tziakas DN, Chalikias GK, Kaski JC, Kekes A, Hatzinikolaou EI, Stakos DA, Tentes IK, Kortsaris AX, Hatseras DI (2007) Inflammatory and anti-inflammatory variable clusters and risk prediction in acute coronary syndrome patients: a factor analysis approach. Atherosclerosis 193(1):196–203CrossRefPubMedGoogle Scholar
  17. 17.
    Stefanadis C, Toutouzas K, Tsiamis E, Vavuranakis M, Tsioufis C, Stefanadi E, Boudoulas H (2007) Relation between local temperature and C-reactive protein levels in patients with coronary artery disease: effects of atorvastatin treatment. Atherosclerosis 192(2): 396–400CrossRefPubMedGoogle Scholar
  18. 18.
    Nishiyama K, Ogawa H, Yasue H, Soejima H, Misumi K, Takazoe K, Yoshimura M, Kugiyama K, Tsuji I, Kumeda K (1998) Simultaneous elevation of the levels of circulating monocyte chemoattractant protein-1 and tissue factor in acute coronary syndromes. Jpn Circ J 62(9):710–712CrossRefPubMedGoogle Scholar
  19. 19.
    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(22): 2117–2124CrossRefPubMedGoogle Scholar
  20. 20.
    Chen MC, Chen CJ, Yang CH, Wu CJ, Fang CY, Hsieh YK, Chang HW (2007) Interleukin-18: a strong predictor of the extent of coronary artery disease in patients with unstable angina. Heart Vessels 22(6):371–375CrossRefPubMedGoogle Scholar
  21. 21.
    Brunetti ND, Munno I, Pellegrino PL, Ruggiero V, Correale M, Cuculo A, De Gennaro L, Campanale G, Mavilio G, Ziccardi L, Di Biase M (2007) Inflammatory cytokine imbalance after coronary angioplasty: links with coronary atherosclerosis. J Interv Cardiol 20(4):248–257CrossRefPubMedGoogle Scholar
  22. 22.
    Pasqui AL, Di Renzo M, Bova G, Maffei S, Pompella G, Auteri A, Puccetti L (2006) Pro-inflammatory/anti-inflammatory cytokine imbalance in acute coronary syndromes. Clin Exp Med 6(1): 38–44CrossRefPubMedGoogle Scholar
  23. 23.
    Jurcut, R, Arsenescu I, Puşcariu T, Uscătescu V, Jurcut, C, Apetrei E, Ginghină C (2005) Is interleukin-18 correlated with endothelial dysfunction and platelet activation in patients with unstable angina? Rom J Intern Med 43(3–4):199–209PubMedGoogle Scholar
  24. 24.
    Halvorsen B, Waehre T, Scholz H, Clausen OP, von der Thüsen JH, Müller F, Heimli H, Tonstad S, Hall C, Frøland SS, Biessen EA, Damås JK, Aukrust P (2005) Interleukin-10 enhances the oxidized LDL-induced foam cell formation of macrophages by antiapoptotic mechanisms. J Lipid Res 46(2):211–219CrossRefPubMedGoogle Scholar
  25. 25.
    van Haelst PL, Tervaert JW, Bijzet J, Baljé-Volkers C, May JF, Langeveld B, Gans RO (2004) Circulating monocytes in patients with acute coronary syndromes lack sufficient interleukin-10 production after lipopolysaccharide stimulation. Clin Exp Immunol 138(2):364–368CrossRefPubMedGoogle Scholar
  26. 26.
    Schindler R, Dinarello CA, Koch KM (1995) Angiotensin-converting-enzyme inhibitors suppress synthesis of tumour necrosis factor and interleukin 1 by human peripheral blood mononuclear cells. Cytokine 7(6):526–533CrossRefPubMedGoogle Scholar
  27. 27.
    Radaelli A, Loardi C, Cazzaniga M, Balestri G, DeCarlini C, Cerrito MG, Cusa EN, Guerra L, Garducci S, Santo D, Menicanti L, Paolini G, Azzellino A, Lavitrano ML, Mancia G, Ferrari AU (2007) Inflammatory activation during coronary artery surgery and its dose-dependent modulation by statin/ACE-inhibitor combination. Arterioscler Thromb Vasc Biol 27(12):2750–2755CrossRefPubMedGoogle Scholar
  28. 28.
    Brili S, Tousoulis D, Antoniades C, Vasiliadou C, Karali M, Papageorgiou N, Ioakeimidis N, Marinou K, Stefanadi E, Stefanadis C (2008) Effects of ramipril on endothelial function and the expression of proinflammatory cytokines and adhesion molecules in young normotensive subjects with successfully repaired coarctation of aorta: a randomized cross-over study. J Am Coll Cardiol 51(7):742–749CrossRefPubMedGoogle Scholar
  29. 29.
    Münzel T, Keaney JF Jr (2001) Are ACE inhibitors a “magic bullet” against oxidative stress? Circulation 104(13):1571–1574CrossRefPubMedGoogle Scholar
  30. 30.
    Vuong AD, Annis LG (2003) Ramipril for the prevention and treatment of cardiovascular disease. Ann Pharmacother 37(3): 412–419CrossRefPubMedGoogle Scholar

Copyright information

© Springer Japan 2010

Authors and Affiliations

  • Huan-qin Chen
    • 1
  • Hong-yong Tan
    • 1
  • Yi-wen Yang
    • 1
  • Lei Qiu
    • 1
  • Xiang-qun Liu
    • 1
    Email author
  1. 1.Department of GeriatricsQi-Lu Hospital of Shandong UniversityJinan, Shandong ProvincePR China

Personalised recommendations