Abstract
Cytokines play a key role in the pathogenesis of coronary artery disease (CAD). The aim of current study was to investigate the relationship between the serum concentrations of 12 cytokines with mortality and extent of CAD in individuals undergoing angiography and healthy controls. 342 CAD patients were recruited and divided into 2 groups: those with ≥50% occlusion in at least one coronary artery [Angiography (+)] or <50% obstruction in coronary arteries [Angiography (−)]. Also 120 healthy subjects were enrolled as control group. Lipid profile, fasting blood glucose, body mass index, and blood pressure were evaluated in all the subjects. An Evidence Investigator® was used for measuring 12 cytokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, MCP-1, IFN-γ, EGF, VEGF) using sandwich chemiluminescent assays. Univariate analysis, multivariate regression models, ROC, and Kaplan–Meier survival curves were used for exploring the candidate markers in CAD patients. Serum level of IFN-γ, IL-4, MCP-1, EGF, IL-6, and IL-8 were markedly higher in angiogram-positive patients, while VEGF concentrations were significantly (P < 0.05) lower, compared to control group. ROC analysis for MCP-1 showed that a cut-off of 61.95 pg/mL had 91% sensitivity and 91% specificity for predicting CAD patients. Moreover, >2.16 pg/mL IL-6 had a > 94% sensitivity and 70% specificity in predicting 2 years mortality in the subjects with a serum MCP-1 > 61.95 pg/ mL, and patients having IL-6/MCP-1 combination had a shorter survival.Our findings demonstrate that CAD patients with serum MCP-1 and IL-6 levels of >61.95 and >2.16 pg/mL had a higher mortality with 94.1% sensitivity and 70.5% specificity for predicting mortality in CAD patients.
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References
Zernecke A, Shagdarsuren E, Weber C (2008) Chemokines in atherosclerosis: an update. Arterioscler Thromb Vasc Biol 28:1897–1908
Martins TB, Anderson JL, Muhlestein JB, Horne BD, Carlquist JF, Roberts WL (2006) Risk factor analysis of plasma cytokines in patients with coronary artery disease by a multiplexed fluorescent immunoassay. Am J Clin Pathol 125:906–913
Martins TB, Anderson JL, Muhlestein JB, Horne BD, Carlquist JF, Roberts WL et al (2006) Risk factor analysis of plasma cytokines in patients with coronary artery disease by a multiplexed fluorescent immunoassay. Am J of clin path 125:906–913
Tousoulis D, Antoniades C, Koumallos N, Stefanadis C (2006) Pro-inflammatory cytokines in acute coronary syndromes: from bench to bedside. Cytokine Growth Factor Rev 17:225–233
Kallio P, Kolehmainen M, Laaksonen DE, Pulkkinen L, Atalay M, Mykkänen H, Uusitupa M, Poutanen K, Niskanen L (2008) Inflammation markers are modulated by responses to diets differing in postprandial insulin responses in individuals with the metabolic syndrome. Am J Clin Nutr 87:1497–1503
Tajfard M, Ghayour Mobarhan M, Rahimi HR, Mouhebati M, Esmaeily H, Ferns GA et al (2014) Anxiety, depression, coronary artery disease and diabetes mellitus; an association study in ghaem hospital, iran. Iran Red Crescent Med J 16:e14589
Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352:1685–1695
Zenti MG, Stefanutti C (2011) Effects of selective H.E.L.P. LDL-apheresis on plasma inflammatory markers concentration in severe dyslipidemia: Implication for anti-inflammatory response. Cytokine 56:850–854
Zakynthinos E, Pappa N (2009) Inflammatory biomarkers in coronary artery disease. J Cardiol 53:317–333
Goswami B, Rajappa M, Mallika V, Shukla DK, Kumar S (2009) TNF-alpha/IL-10 ratio and C-reactive protein as markers of the inflammatory response in CAD-prone North Indian patients with acute myocardial infarction. Clin Chim Acta 408:14–18
Mirhafez S, Zarifian A, Ebrahimi M, Ali R, Avan A, Tajfard M, et al (2015) Relationship between serum cytokine and growth factor concentrations and coronary artery disease. Clin Biochem 48:575–580
Zomorrodian D, Khajavi-Rad A, Avan A, Ebrahimi M, Nematy M, Azarpazhooh MR et al (2015) Metabolic syndrome components as markers to prognosticate the risk of developing chronic kidney disease: evidence-based study with 6492 individuals. J Epidemiol Community Health 69:594–598
Mirhafez SR, Pasdar A, Avan A, Esmaily H, Moezzi A, Mohebati M et al (2015) Cytokine and growth factor profiling in patients with the metabolic syndrome. Br J Nutr 113:1911–1919
Mirhafez SR, Mohebati M, Feiz Disfani M, Saberi Karimian M, Ebrahimi M, Avan A et al (2014) An imbalance in serum concentrations of inflammatory and anti-inflammatory cytokines in hypertension. J Am Soc Hypertens 8:614–623
Libby P, Ridker PM, Maseri A (2002) Inflammation and atherosclerosis. Circulation 105:1135–1143
Tajfard M, Latiff LA, Rahimi HR, Mouhebati M, Esmaeily H, Taghipour A, et al (2014) Serum inflammatory cytokines and depression in coronary artery disease. Iran Red Crescent Med J 16:e17111
Wojciak-Stothard B, Entwistle A, Garg R, Ridley AJ (1998) Regulation of TNF-alpha-induced reorganization of the actin cytoskeleton and cell-cell junctions by Rho, Rac, and Cdc42 in human endothelial cells. J Cell Physiol 176:150–165
Schieffer B, Selle T, Hilfiker A, Hilfiker-Kleiner D, Grote K, Tietge UJ et al (2004) Impact of interleukin-6 on plaque development and morphology in experimental atherosclerosis. Circulation 110:3493–3500
Elhage R, Clamens S, Besnard S, Mallat Z, Tedgui A, Arnal J et al (2001) Involvement of interleukin-6 in atherosclerosis but not in the prevention of fatty streak formation by 17beta-estradiol in apolipoprotein E-deficient mice. Atherosclerosis 156:315–320
Merhi-Soussi F, Kwak BR, Magne D, Chadjichristos C, Berti M, Pelli G et al (2005) Interleukin-1 plays a major role in vascular inflammation and atherosclerosis in male apolipoprotein E-knockout mice. Cardiovasc Res 66:583–593
Celletti FL, Waugh JM, Amabile PG, Brendolan A, Hilfiker PR, Dake MD (2001) Vascular endothelial growth factor enhances atherosclerotic plaque progression. Nat Med 7:425–429
Blann AD, Belgore FM, McCollum CN, Silverman S, Lip PL, Lip GY (2002) Vascular endothelial growth factor and its receptor, Flt-1, in the plasma of patients with coronary or peripheral atherosclerosis, or Type II diabetes. Clin Sci 102:187–194
Alber HF, Frick M, Dulak J, Dorler J, Zwick RH, Dichtl W et al (2005) Vascular endothelial growth factor (VEGF) plasma concentrations in coronary artery disease. Heart 91:365–366
de Lemos JA, Morrow DA, Sabatine MS, Murphy SA, Gibson CM, Antman EM et al (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
Hoogeveen RC, Morrison A, Boerwinkle E, Miles JS, Rhodes CE, Sharrett AR et al (2005) Plasma MCP-1 level and risk for peripheral arterial disease and incident coronary heart disease: atherosclerosis Risk in Communities study. Atherosclerosi 183: 301–307
Khan DA, Ansari WM, Khan FA (2011) Pro/anti-inflammatory cytokines in the pathogenesis of premature coronary artery disease. J Interferon Cytokine Res 31:561–567
Schuijf JD, Pundziute G, Jukema JW, Lamb HJ, van der Hoeven BL, de Roos A et al (2006) Diagnostic accuracy of 64-slice multislice computed tomography in the noninvasive evaluation of significant coronary artery disease. Am J Cardiol 98:145–148
Biancari F, Lahtinen J, Salmela E, Niemela M, Pokela R, Rainio P et al (2003) Does angiographic severity of coronary artery disease predict postoperative outcome after coronary artery bypass surgery? Scand Cardiovasc J 37:275–282
Acknowledgements
The Mashhad University of Medical Science Research Council supported this research (Fund Number MUMS/900671). This study is the subject thesis of Mr. Mohammad Tajfard, which is the PhD Candidate of the community health in University Putra Malaysia. Authors would like to thank Center for International Scientific Studies and Collaboration for their support.
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Tajfard, M., Latiff, L.A., Rahimi, H.R. et al. Serum concentrations of MCP-1 and IL-6 in combination predict the presence of coronary artery disease and mortality in subjects undergoing coronary angiography. Mol Cell Biochem 435, 37–45 (2017). https://doi.org/10.1007/s11010-017-3054-5
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DOI: https://doi.org/10.1007/s11010-017-3054-5