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Review

Anti-inflammatory drugs as promising cardiovascular treatments

, , , &
Pages 109-125 | Received 31 Oct 2016, Accepted 14 Dec 2016, Published online: 28 Dec 2016

References

  • Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005 Apr 21;352(16):1685–1695.
  • Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature. 2011 May 19; 473(7347):317–325.
  • Ghattas A, Griffiths HR, Devitt A, et al. Monocytes in coronary artery disease and atherosclerosis: where are we now? J Am Coll Cardiol. 2013 Oct 22;62(17):1541–1551.
  • Swirski FK, Nahrendorf M. Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure. Science. 2013 Jan 11;339(6116):161–166.
  • Libby P. Current concepts of the pathogenesis of the acute coronary syndromes. Circulation. 2001 Jul 17;104(3):365–372.
  • Liuzzo G, Biasucci LM, Gallimore JR, et al. The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. N Engl J Med. 1994 Aug 18;331(7):417–424.
  • Braunwald E. Creating controversy where none exists: the important role of C-reactive protein in the care, afcaps/texcaps, prove it, reversal, a to z, jupiter, heart protection, and ascot trials. Eur Heart J. 2012 Feb;33(4):430–432.
  • Ridker PM, Danielson E, Fonseca FAH, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008 Nov 20;359(21):2195–2207.
  • Roubille F, Cayla G, Picot M-C, et al. [C-reactive protein (CRP) after revascularized STEMI: is CRP a prognostic factor?]. Rev Médecine Interne Fondée Par Société Natl Francaise Médecine Interne. 2008 Nov;29(11):868–874.
  • Ridker PM, Rifai N, Stampfer MJ, et al. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation. 2000 Apr 18;101(15):1767–1772.
  • Morrow DA, Ridker PM. C-reactive protein, inflammation, and coronary risk. Med Clin North Am. 2000 Jan;84(1):149–61, ix.
  • Maier W, Altwegg LA, Corti R, et al. Inflammatory markers at the site of ruptured plaque in acute myocardial infarction: locally increased interleukin-6 and serum amyloid A but decreased C-reactive protein. Circulation. 2005 Mar 22;111(11):1355–1361.
  • Kaptoge S, Seshasai SRK, Gao P, et al. Inflammatory cytokines and risk of coronary heart disease: new prospective study and updated meta-analysis. Eur Heart J. 2014 Mar;35(9):578–589.
  • Interleukin-6 Receptor Mendelian Randomisation Analysis (IL6R MR) Consortium. The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis. Lancet Lond Engl. 2012 Mar 31;379(9822):1214–1224.
  • Ikeda Y, Shimada K, Teramoto T, et al. Low-dose aspirin for primary prevention of cardiovascular events in Japanese patients 60 years or older with atherosclerotic risk factors: a randomized clinical trial. Jama. 2014 Dec 17;312(23):2510–2520.
  • Roubille F, Tardif J-C. Anti-inflammatory drugs and the heart. Anti-Inflamm Anti-Allergy Agents Med Chem. 2013;12(1):2.
  • Su M-I, Chen C-Y, Yeh H-I, et al. Concise review of optical coherence tomography in clinical practice. Acta Cardiol Sin. 2016 Jul;32(4):381–386.
  • Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation. 1995 Aug 1;92(3):657–671.
  • Ambrose JA, Tannenbaum MA, Alexopoulos D, et al. Angiographic progression of coronary artery disease and the development of myocardial infarction. J Am Coll Cardiol. 1988 Jul;12(1):56–62.
  • Stary HC, Chandler AB, Dinsmore RE, et al. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the committee on vascular lesions of the council on arteriosclerosis, american heart association. Arterioscler Thromb Vasc Biol. 1995 Sep;15(9):1512–1531.
  • Waxman S, Ishibashi F, Muller JE. Detection and treatment of vulnerable plaques and vulnerable patients: novel approaches to prevention of coronary events. Circulation. 2006 Nov 28;114(22):2390–2411.
  • Moselewski F, Ropers D, Pohle K, et al. Comparison of measurement of cross-sectional coronary atherosclerotic plaque and vessel areas by 16-slice multidetector computed tomography versus intravascular ultrasound. Am J Cardiol. 2004 Nov 15;94(10):1294–1297.
  • Lin E, Alessio A. What are the basic concepts of temporal, contrast, and spatial resolution in cardiac CT?. J Cardiovasc Comput Tomogr. 2009;3(6):403-408. doi:10.1016/j.jcct.2009.07.003.
  • Hyafil F, Cornily J-C, Feig JE, et al. Noninvasive detection of macrophages using a nanoparticulate contrast agent for computed tomography. Nat Med. 2007 May;13(5):636–641.
  • Hyafil F, Cornily J-C, Rudd JHF, et al. Quantification of inflammation within rabbit atherosclerotic plaques using the macrophage-specific CT contrast agent N1177: a comparison with 18F-FDG PET/CT and histology. J Nucl Med Off Publ Soc Nucl Med. 2009 Jun;50(6):959–965.
  • Fayad ZA. The assessment of the vulnerable atherosclerotic plaque using MR imaging: a brief review. Int J Cardiovasc Imaging. 2001 Jun;17(3):165–177.
  • Trivedi RA, Mallawarachi C, U-King-Im J-M, et al. Identifying inflamed carotid plaques using in vivo USPIO-enhanced MR imaging to label plaque macrophages. Arterioscler Thromb Vasc Biol. 2006 Jul;26(7):1601–1606.
  • Tang TY, Howarth SPS, Miller SR, et al. The ATHEROMA (Atorvastatin Therapy: effects on Reduction of Macrophage Activity) study. evaluation using ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging in carotid disease. J Am Coll Cardiol. 2009 Jun 2;53(22):2039–2050.
  • Joshi NV, Vesey AT, Williams MC, et al. 18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial. Lancet Lond Engl. 2014 Feb 22;383(9918):705–713.
  • Rominger A, Saam T, Vogl E, et al. In vivo imaging of macrophage activity in the coronary arteries using 68Ga-DOTATATE PET/CT: correlation with coronary calcium burden and risk factors. J Nucl Med Off Publ Soc Nucl Med. 2010 Feb;51(2):193–197.
  • Dweck MR, Chow MWL, Joshi NV, et al. Coronary arterial 18F-sodium fluoride uptake: a novel marker of plaque biology. J Am Coll Cardiol. 2012 Apr 24;59(17):1539–1548.
  • Hoang V, Grounds J, Pham D, et al. The role of intracoronary plaque imaging with intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy in patients with coronary artery disease. Curr Atheroscler Rep. 2016 Sep;18(9):57.
  • Bourantas CV, Jaffer FA, Gijsen FJ, et al. Hybrid intravascular imaging: recent advances, technical considerations, and current applications in the study of plaque pathophysiology. Eur Heart J. 2016 Apr 26. pii: ehw097. [Epub ahead of print].
  • Pathan F, Negishi K. Prediction of cardiovascular outcomes by imaging coronary atherosclerosis. Cardiovasc Diagn Ther. 2016 Aug;6(4):322–339.
  • Paramel Varghese G, Folkersen L, Strawbridge RJ, et al. NLRP3 inflammasome expression and activation in human atherosclerosis. J Am Heart Assoc. 2016 May;5(5):e003031. doi:10.1161/JAHA.115.003031.
  • Rajamäki K, Mäyränpää MI, Risco A, et al. p38δ MAPK: A novel regulator of nlrp3 inflammasome activation with increased expression in coronary atherogenesis. Arterioscler Thromb Vasc Biol. 2016 Sep;36(9):1937-1946. doi: 10.1161/ATVBAHA.115.307312.
  • Libby P, Warner SJ, Friedman GB. Interleukin 1: a mitogen for human vascular smooth muscle cells that induces the release of growth-inhibitory prostanoids. J Clin Invest. 1988 Feb;81(2):487–498.
  • Bevilacqua MP, Pober JS, Majeau GR, et al. Interleukin 1 (IL-1) induces biosynthesis and cell surface expression of procoagulant activity in human vascular endothelial cells. J Exp Med. 1984 Aug 1;160(2):618–623.
  • Ridker PM, Howard CP, Walter V, et al. Effects of interleukin-1β inhibition with canakinumab on hemoglobin A1c, lipids, C-reactive protein, interleukin-6, and fibrinogen: a phase IIb randomized, placebo-controlled trial. Circulation. 2012 Dec 4;126(23):2739–2748.
  • Ridker PM, Thuren T, Zalewski A, et al. Interleukin-1β inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). Am Heart J. 2011 Oct;162(4):597–605.
  • Roubille F, Busseuil D, Shi Y, et al. The interleukin-1β modulator gevokizumab reduces neointimal proliferation and improves reendothelialization in a rat carotid denudation model. Atherosclerosis. 2014 Oct;236(2):277–285.
  • Choudhury RP, Birks JS, Mani V, et al. Arterial effects of canakinumab in patients with atherosclerosis and type 2 diabetes or glucose intolerance. J Am Coll Cardiol. 2016 Oct 18;68(16):1769–1780.
  • Lee TS, Yen HC, Pan CC, et al. The role of interleukin 12 in the development of atherosclerosis in ApoE-deficient mice. Arterioscler Thromb Vasc Biol. 1999 Mar;19(3):734–742.
  • Espígol-Frigolé G, Planas-Rigol E, Ohnuki H, et al. Identification of IL-23p19 as an endothelial proinflammatory peptide that promotes gp130-STAT3 signaling. Sci Signal. 2016 Mar 15;9(419):ra28.
  • Cheng X, Yu X, Ding Y-J, et al. The Th17/Treg imbalance in patients with acute coronary syndrome. Clin Immunol Orlando Fla. 2008 Apr;127(1):89–97.
  • Langley RG, Papp K, Gottlieb AB, et al. Safety results from a pooled analysis of randomized, controlled phase II and III clinical trials and interim data from an open-label extension trial of the interleukin-12/23 monoclonal antibody, briakinumab, in moderate to severe psoriasis. J Eur Acad Dermatol Venereol JEADV. 2013 Oct;27(10):1252–1261.
  • Ryan C, Leonardi CL, Krueger JG, et al. Association between biologic therapies for chronic plaque psoriasis and cardiovascular events: a meta-analysis of randomized controlled trials. Jama. 2011 Aug 24;306(8):864–871.
  • Gulliver WP, Randell S, Gulliver S, et al. Do biologics protect patients with psoriasis from myocardial infarction? a retrospective cohort. J Cutan Med Surg. 2016 May 10.
  • Wallberg-Jonsson S, Ohman ML, Dahlqvist SR. Cardiovascular morbidity and mortality in patients with seropositive rheumatoid arthritis in Northern Sweden. J Rheumatol. 1997 Mar;24(3):445–451.
  • Signorelli SS, Candido S, Salemi R, et al. Low levels of inflammation and the absence of subclinical atherosclerosis in rheumatoid arthritis. Mol Med Rep. 2016 Apr;13(4):3521–3524.
  • Dixon WG, Watson KD, Lunt M,,, et al. Reduction in the incidence of myocardial infarction in patients with rheumatoid arthritis who respond to anti-tumor necrosis factor alpha therapy: results from the British society for rheumatology biologics register. Arthritis Rheum. 2007 Sep; 56(9):2905–2912.
  • Jacobsson LTH, Turesson C, Gülfe A, et al. Treatment with tumor necrosis factor blockers is associated with a lower incidence of first cardiovascular events in patients with rheumatoid arthritis. J Rheumatol. 2005 Jul;32(7):1213–1218.
  • Liu C-L, Xue Z-Q, Gao S-P, et al. The relationship between interleukin-6 promotor polymorphisms and slow coronary flow phenomenon. Clin Lab. 2016;62(5):947–953.
  • Nus M, Mallat Z. Immune-mediated mechanisms of atherosclerosis and implications for the clinic. Expert Rev Clin Immunol. 2016 Nov;12(11):1217–1237.
  • Strang AC, Bisoendial RJ, Kootte RS, et al. Pro-atherogenic lipid changes and decreased hepatic LDL receptor expression by tocilizumab in rheumatoid arthritis. Atherosclerosis. 2013 Jul;229(1):174–181.
  • Madhur MS, Funt SA, Li L, et al. ROLE OF INTERLEUKIN 17 IN INFLAMMATION, ATHEROSCLEROSIS AND VASCULAR FUNCTION IN APOLIPOPROTEIN E-DEFICIENT MICE. Arterioscler Thromb Vasc Biol. 2011 Jul.
  • De Boer OJ, Van Der Meer JJ, Teeling P, et al. Differential expression of interleukin-17 family cytokines in intact and complicated human atherosclerotic plaques. J Pathol. 2010 Mar;220(4):499–508.
  • Rao LN, Ponnusamy T, Philip S, et al. Hypercholesterolemia induced immune response and inflammation on progression of atherosclerosis in apob(tm2sgy) ldlr(tm1her)/j mice. Lipids. 2015 Aug;50(8):785–797.
  • Potekhina AV, Pylaeva E, Provatorov S, et al. Treg/Th17 balance in stable CAD patients with different stages of coronary atherosclerosis. Atherosclerosis. 2015 Jan;238(1):17–21.
  • Van Dijk RA, Duinisveld AJF, Schaapherder AF, et al. A change in inflammatory footprint precedes plaque instability: a systematic evaluation of cellular aspects of the adaptive immune response in human atherosclerosis. J Am Heart Assoc. 2015;4(4):e001403. doi:10.1161/JAHA.114.001403.
  • Chai M, Ji Q, Zhang H, et al. The protective effect of interleukin-37 on vascular calcification and atherosclerosis in apolipoprotein e-deficient mice with diabetes. J Interferon Cytokine Res Off J Int Soc Interferon Cytokine Res. 2015 Jul;35(7):530–539.
  • Wang X, Cai X, Chen L, et al. The evaluation of plasma and leukocytic IL-37 expression in early inflammation in patients with acute ST-segment elevation myocardial infarction after PCI. Mediators Inflamm. 2015;2015:626934.
  • Huang J, Hou FL, Zhang AY, et al. Protective effect of the polarity of macrophages regulated by IL-37 on atherosclerosis. Genet Mol Res GMR. 2016 May 13;15(2). doi: 10.4238/gmr.15027616.
  • Casas R, Sacanella E, Urpí-Sardà M, et al. Long-term immunomodulatory effects of a mediterranean diet in adults at high risk of cardiovascular disease in the prevencion con dieta mediterranea randomized controlled trial. J Nutr. 2016 Sep;146(9):1684-1693. doi: 10.3945/jn.115.229476.
  • Weber C, Schober A, Zernecke A. Chemokines: key regulators of mononuclear cell recruitment in atherosclerotic vascular disease. Arterioscler Thromb Vasc Biol. 2004 Nov;24(11):1997–2008.
  • Podolec J, Kopec G, Niewiara L, et al. Chemokine RANTES is increased at early stages of coronary artery disease. J Physiol Pharmacol Off J Pol Physiol Soc. 2016 Apr;67(2):321–328.
  • Koenen RR, Weber C. Chemokines: established and novel targets in atherosclerosis. EMBO Mol Med. 2011 Dec;3(12):713–725.
  • Zungsontiporn N, Tello RR, Zhang G, et al. Non-classical monocytes and monocyte chemoattractant protein-1 (mcp-1) correlate with coronary artery calcium progression in chronically hiv-1 infected adults on stable antiretroviral therapy. Plos One. 2016;11(2):e0149143.
  • Rottman JB, Ganley KP, Williams K, et al. Cellular localization of the chemokine receptor CCR5. Correlation to cellular targets of HIV-1 infection. Am J Pathol. 1997 Nov;151(5):1341–1351.
  • Zernecke A, Weber C. Chemokines in atherosclerosis proceedings resumed. Arterioscler Thromb Vasc Biol. 2014 Apr 1;34(4):742–750.
  • Jiang W, Cen Y, Song Y, et al. Artesunate attenuated progression of atherosclerosis lesion formation alone or combined with rosuvastatin through inhibition of pro-inflammatory cytokines and pro-inflammatory chemokines. Phytomedicine Int J Phytother Phytopharm. 2016 Oct 15;23(11):1259–1266.
  • Gilbert J, Lekstrom-Himes J, Donaldson D, et al. Effect of CC chemokine receptor 2 CCR2 blockade on serum C-reactive protein in individuals at atherosclerotic risk and with a single nucleotide polymorphism of the monocyte chemoattractant protein-1 promoter region. Am J Cardiol. 2011 Mar 15;107(6):906–911.
  • Cipriani S, Francisci D, Mencarelli A, et al. Efficacy of the CCR5 antagonist maraviroc in reducing early, ritonavir-induced atherogenesis and advanced plaque progression in mice. Circulation. 2013 May 28;127(21):2114–2124.
  • Piconi S, Pocaterra D, Rainone V, et al. Maraviroc reduces arterial stiffness in pi-treated hiv-infected patients. Sci Rep. 2016;6:28853.
  • McEver RP. Selectins: lectins that initiate cell adhesion under flow. Curr Opin Cell Biol. 2002 Oct;14(5):581–586.
  • Scialla JJ, Plantinga LC, Kao WHL, et al. Soluble P-selectin levels are associated with cardiovascular mortality and sudden cardiac death in male dialysis patients. Am J Nephrol. 2011;33(3):224–230.
  • Dong ZM, Chapman SM, Brown AA, et al. The combined role of P- and E-selectins in atherosclerosis. J Clin Invest. 1998 Jul 1;102(1):145–152.
  • Riad A, Du J, Stiehl S, et al. Low-dose treatment with atorvastatin leads to anti-oxidative and anti-inflammatory effects in diabetes mellitus. Eur J Pharmacol. 2007 Aug 27;569(3):204–211.
  • Stähli BE, Tardif J-C, Carrier M, et al. Effects of p-selectin antagonist inclacumab in patients undergoing coronary artery bypass graft surgery: select-cabg trial. J Am Coll Cardiol. 2016 Jan 26;67(3):344–346. doi: 10.1016/j.jacc.2015.10.071.
  • Ridker PM, Hennekens CH, Roitman-Johnson B, et al. Plasma concentration of soluble intercellular adhesion molecule 1 and risks of future myocardial infarction in apparently healthy men. Lancet Lond Engl. 1998 Jan 10;351(9096):88–92.
  • Klemann C, Wagner L, Stephan M, et al. Cut to the chase: a review of CD26/dipeptidyl peptidase-4’s (DPP4) entanglement in the immune system. Clin Exp Immunol. 2016 Jul;185(1):1–21.
  • Hwang H-J, Chung HS, Jung TW, et al. The dipeptidyl peptidase-IV inhibitor inhibits the expression of vascular adhesion molecules and inflammatory cytokines in HUVECs via Akt- and AMPK-dependent mechanisms. Mol Cell Endocrinol. 2015 Apr;15(405):25–34.
  • Ding S, Du Y-P, Lin N, et al. Effect of glucagon-like peptide-1 on major cardiovascular outcomes in patients with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials. International Journal of Cardiology. 2016 Nov 1;222:957–962.
  • Roubille F, Kritikou E, Busseuil D, et al. Colchicine: an old wine in a new bottle? Anti-Inflamm Anti-Allergy Agents Med Chem. 2013;12(1):14–23.
  • Demidowich AP, Davis AI, Dedhia N, et al. Colchicine to decrease NLRP3-activated inflammation and improve obesity-related metabolic dysregulation. Med Hypotheses. 2016 Jul;92:67–73.
  • Crittenden DB, Lehmann RA, Schneck L, et al. Colchicine use is associated with decreased prevalence of myocardial infarction in patients with gout. J Rheumatol. 2012 Jul;39(7):1458–1464.
  • Nidorf SM, Eikelboom JW, Budgeon CA, et al. Low-dose colchicine for secondary prevention of cardiovascular disease. J Am Coll Cardiol. 2013 Jan 29; 61(4):404–410.
  • Verma S, Eikelboom JW, Nidorf SM, et al. Colchicine in cardiac disease: a systematic review and meta-analysis of randomized controlled trials. BMC Cardiovasc Disord. 2015;15:96.
  • Westlake SL, Colebatch AN, Baird J, et al. The effect of methotrexate on cardiovascular disease in patients with rheumatoid arthritis: a systematic literature review. Rheumatol Oxf Engl. 2010 Feb;49(2):295–307.
  • Roubille C, Richer V, Starnino T, et al. The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis. Ann Rheum Dis. 2015 Mar;74(3):480-489. doi: 10.1136/annrheumdis-2014-206624.
  • Wessels JAM, Huizinga TWJ, Guchelaar H-J. Recent insights in the pharmacological actions of methotrexate in the treatment of rheumatoid arthritis. Rheumatol Oxf Engl. 2008 Mar;47(3):249–255.
  • Micha R, Imamura F, Wyler Von Ballmoos M, et al. Systematic review and meta-analysis of methotrexate use and risk of cardiovascular disease. Am J Cardiol. 2011 Nov 1;108(9):1362–1370.
  • Kim H-J, Kim M-J, Lee C-K, et al. Effects of methotrexate on carotid intima-media thickness in patients with rheumatoid arthritis. J Korean Med Sci. 2015 Nov;30(11):1589–1596.
  • Rajamäki K, Lappalainen J, Oörni K, et al. Cholesterol crystals activate the NLRP3 inflammasome in human macrophages: a novel link between cholesterol metabolism and inflammation. Plos One. 2010;5(7):e11765.
  • Glynn RJ, Danielson E, Fonseca FAH, et al. A randomized trial of rosuvastatin in the prevention of venous thromboembolism. N Engl J Med. 2009 Apr 30;360(18):1851–1861.
  • Ridker PM, Rifai N, Pfeffer MA, et al. Long-term effects of pravastatin on plasma concentration of C-reactive protein. The cholesterol and recurrent events (care) investigators. Circulation. 1999 Jul 20;100(3):230–235.
  • Chu AY, Guilianini F, Barratt BJ, et al. Pharmacogenetic determinants of statin-induced reductions in C-reactive protein. Circ Cardiovasc Genet. 2012 Feb 1;5(1):58–65.
  • Banach M, Serban C, Sahebkar A, et al. Impact of statin therapy on coronary plaque composition: a systematic review and meta-analysis of virtual histology intravascular ultrasound studies. BMC Med. 2015;13:229.
  • Ridker PM, Danielson E, Fonseca FA, et al. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet Lond Engl. 2009 Apr 4;373(9670):1175–1182.
  • Murphy SA, Cannon CP, Blazing MA, et al. Reduction in total cardiovascular events with ezetimibe/simvastatin post-acute coronary syndrome: the IMPROVE-IT trial. J Am Coll Cardiol. 2016 Feb 2;67(4):353–361.
  • Bohula EA, Giugliano RP, Cannon CP, et al. Achievement of dual low-density lipoprotein cholesterol and high-sensitivity C-reactive protein targets more frequent with the addition of ezetimibe to simvastatin and associated with better outcomes in IMPROVE-IT. Circulation. 2015 Sep 29;132(13):1224–1233.
  • Tie C, Gao K, Zhang N, et al. Ezetimibe attenuates atherosclerosis associated with lipid reduction and inflammation inhibition. Plos One. 2015;10(11):e0142430.
  • Giunzioni I, Tavori H, Covarrubias R, et al. Local effects of human PCSK9 on the atherosclerotic lesion. J Pathol. 2016 Jan;238(1):52–62.
  • Feingold KR, Moser AH, Shigenaga JK, et al. Inflammation stimulates the expression of PCSK9. Biochem Biophys Res Commun. 2008 Sep 19;374(2):341–344.
  • Dwivedi DJ, Grin PM, Khan M, et al. Differential expression of pcsk9 modulates infection, inflammation and coagulation in a murine model of sepsis. Shock Augusta Ga. 2016 Dec;46(6):672-680.
  • Cheng JM, Oemrawsingh RM, Garcia-Garcia HM, et al. PCSK9 in relation to coronary plaque inflammation: results of the ATHEROREMO-IVUS study. Atherosclerosis. 2016;248:117–122.
  • Robinson JG, Farnier M, Krempf M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med [Internet]. 2015 avril;372(16):1489–1499.
  • Sahebkar A, Di Giosia P, Stamerra CA, et al. Effect of monoclonal antibodies to PCSK9 on high-sensitivity C-reactive protein levels: a meta-analysis of 16 randomized controlled treatment arms. Br J Clin Pharmacol. 2016 Jun;81(6):1175–1190.
  • Cirera S, Tørsleff BCJ, Ritz C, et al. Hepatic expression of inflammatory genes and microRNAs in pigs with high “cholesteryl ester transfer protein” (CETP) activity. Mamm Genome Off J Int Mamm Genome Soc. 2016 Oct;27(9–10):503–510.
  • Mani V, Woodward M, Samber D, et al. Predictors of change in carotid atherosclerotic plaque inflammation and burden as measured by 18-FDG-PET and MRI, respectively, in the dal-PLAQUE study. Int J Cardiovasc Imaging. 2014 Mar;30(3):571–582.
  • Schwartz GG, Olsson AG, Abt M, et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med. 2012 Nov 29;367(22):2089–2099.
  • Tardif J-C, Rhainds D, Brodeur M, et al. Genotype-dependent effects of dalcetrapib on cholesterol efflux and inflammation: concordance with clinical outcomes. Circ Cardiovasc Genet. 2016 Aug;9(4):340–348.
  • Arslan F, De Kleijn DP, Pasterkamp G. Innate immune signaling in cardiac ischemia. Nat Rev Cardiol. 2011 May;8(5):292–300.
  • Roubille F, Lacampagne A. New drug avenues for cardioprotection in patients with acute myocardial infarction. Am J Cardiovasc Drugs Drugs Devices Interv. 2014 Feb;14(1):73–77.
  • Roubille F, Tardif J-C. Inflammation and the heart - prime time for new therapeutic approaches. Expert Opin Emerg Drugs. 2013 Sep;18(3):259–261.
  • Sadowski M, Ząbczyk M, Undas A. Coronary thrombus composition: links with inflammation, platelet and endothelial markers. Atherosclerosis. 2014 Dec;237(2):555–561.
  • Adlbrecht C, Wurm R, Humenberger M, et al. Peri-interventional endothelin–a receptor blockade improves long-term outcome in patients with ST-elevation acute myocardial infarction. Thromb Haemost. 2014 Jul 3;112(1):176–182.
  • Van Diepen S, Newby LK, Lopes RD, et al. Prognostic relevance of baseline pro- and anti-inflammatory markers in STEMI: an APEX AMI substudy. Int J Cardiol. 2013 Oct 3;168(3):2127–2133.
  • Marchant DJ, Boyd JH, Lin DC, et al. Inflammation in myocardial diseases. Circ Res. 2012 Jan 6;110(1):126–144.
  • Kumar AG, Ballantyne CM, Michael LH, et al. Induction of monocyte chemoattractant protein-1 in the small veins of the ischemic and reperfused canine myocardium. Circulation. 1997 Feb 4;95(3):693–700.
  • Gerard C, Rollins BJ. Chemokines and disease. Nat Immunol. 2001 Feb;2(2):108–115.
  • Frangogiannis NG, Smith CW, Entman ML. The inflammatory response in myocardial infarction. Cardiovasc Res. 2002 Jan;53(1):31–47.
  • Frangogiannis NG, Mendoza LH, Lewallen M, et al. Induction and suppression of interferon-inducible protein 10 in reperfused myocardial infarcts may regulate angiogenesis. FASEB J Off Publ Fed Am Soc Exp Biol. 2001 Jun;15(8):1428–1430.
  • Frangogiannis NG, Mendoza LH, Lindsey ML, et al. IL-10 is induced in the reperfused myocardium and may modulate the reaction to injury. J Immunol Baltim Md 1950. 2000 Sep 1;165(5):2798–2808.
  • Nahrendorf M, Pittet MJ, Swirski FK. Monocytes: protagonists of infarct inflammation and repair after myocardial infarction. Circulation. 2010 Jun 8;121(22):2437–2445.
  • Yellon DM, Hausenloy DJ. Myocardial reperfusion injury. N Engl J Med. 2007 Sep 13;357(11):1121–1135.
  • Nahrendorf M, Swirski FK, Aikawa E, et al. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med. 2007 Nov 26;204(12):3037–3047.
  • Maekawa Y, Mizue N, Chan A, et al. Survival and cardiac remodeling after myocardial infarction are critically dependent on the host innate immune interleukin-1 receptor-associated kinase-4 signaling: a regulator of bone marrow-derived dendritic cells. Circulation. 2009 Oct 6;120(14):1401–1414.
  • Anzai A, Anzai T, Nagai S, et al. Regulatory role of dendritic cells in postinfarction healing and left ventricular remodeling. Circulation. 2012 Mar 13;125(10):1234–1245.
  • Lee WW, Marinelli B, Van Der Laan AM, et al. PET/MRI of inflammation in myocardial infarction. J Am Coll Cardiol. 2012 Jan 10;59(2):153–163.
  • Rischpler C, Dirschinger RJ, Nekolla SG, et al. prospective evaluation of 18f-fluorodeoxyglucose uptake in postischemic myocardium by simultaneous positron emission tomography/magnetic resonance imaging as a prognostic marker of functional outcome. Circ Cardiovasc Imaging. 2016 Apr;9(4):e004316.
  • Wollenweber T, Roentgen P, Schäfer A, et al. Characterizing the inflammatory tissue response to acute myocardial infarction by clinical multimodality noninvasive imaging. Circ Cardiovasc Imaging. 2014 Sep;7(5):811–818.
  • Lautamäki R, Schuleri KH, Sasano T, et al. Integration of infarct size, tissue perfusion, and metabolism by hybrid cardiac positron emission tomography/computed tomography: evaluation in a porcine model of myocardial infarction. Circ Cardiovasc Imaging. 2009 Jul;2(4):299–305.
  • Carbone F, Crowe LA, Roth A, et al. Treatment with anti-RANKL antibody reduces infarct size and attenuates dysfunction impacting on neutrophil-mediated injury. J Mol Cell Cardiol. 2016;94:82–94.
  • Sheu -J-J, Sung P-H, Leu S, et al. Innate immune response after acute myocardial infarction and pharmacomodulatory action of tacrolimus in reducing infarct size and preserving myocardial integrity. J Biomed Sci. 2013;20:82.
  • Tardif J-C, Tanguay J-F, Wright SR, et al. Effects of the P-selectin antagonist inclacumab on myocardial damage after percutaneous coronary intervention for non-ST-segment elevation myocardial infarction: results of the SELECT-ACS trial. J Am Coll Cardiol. 2013 May 21;61(20):2048–2055.
  • Yudkin JS, Richter B, Gale EAM. Intensified glucose lowering in type 2 diabetes: time for a reappraisal. Diabetologia. 2010 Oct;53(10):2079–2085.
  • Control Group, Turnbull FM, Abraira C, Anderson RJ, et al. Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia. 2009 Nov;52(11):2288–2298.
  • Kahles F, Meyer C, Möllmann J, et al. GLP-1 secretion is increased by inflammatory stimuli in an IL-6-dependent manner, leading to hyperinsulinemia and blood glucose lowering. Diabetes. 2014 Oct;63(10):3221–3229.
  • Marques C, Mega C, Gonçalves A, et al. Sitagliptin prevents inflammation and apoptotic cell death in the kidney of type 2 diabetic animals. Mediators Inflamm. 2014;2014:538737.
  • Younce CW, Burmeister MA, Ayala JE. Exendin-4 attenuates high glucose-induced cardiomyocyte apoptosis via inhibition of endoplasmic reticulum stress and activation of SERCA2a. Am J Physiol Cell Physiol. 2013 Mar;304(6):C508–18.
  • Younce CW, Niu J, Ayala J, et al. Exendin-4 improves cardiac function in mice overexpressing monocyte chemoattractant protein-1 in cardiomyocytes. J Mol Cell Cardiol. 2014;76:172–176.
  • Sokos GG, Nikolaidis LA, Mankad S, et al. Glucagon-like peptide-1 infusion improves left ventricular ejection fraction and functional status in patients with chronic heart failure. J Card Fail. 2006 Dec;12(9):694–699.
  • Lønborg J, Vejlstrup N, Kelbæk H, et al. Exenatide reduces reperfusion injury in patients with ST-segment elevation myocardial infarction. Eur Heart J. 2012 Jun;33(12):1491–1499.
  • Woo JS, Kim W, Ha SJ, et al. Cardioprotective effects of exenatide in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention: results of exenatide myocardial protection in revascularization study. Arterioscler Thromb Vasc Biol. 2013 Sep;33(9):2252–2260.
  • Roos S, Timmers L, Van Hout GP, et al. TCT-231 exenatide does not improve myocardial salvage in patients with an acute myocardial infarction successfully treated with primary percutaneous coronary intervention: the first results of the exami trial. J Am Coll Cardiol. 2015 Oct 13. Available from: https://www.researchgate.net/publication/283036268_TCT-231_Exenatide_Does_Not_Improve_Myocardial_Salvage_In_Patients_With_An_Acute_Myocardial_Infarction_Successfully_Treated_With_Primary_Percutaneous_Coronary_Intervention_The_First_Results_Of_The_EXAM
  • Anderluh M, Kocic G, Tomovic K, et al. Cross-talk between the dipeptidyl peptidase-4 and stromal cell-derived factor-1 in stem cell homing and myocardial repair: potential impact of dipeptidyl peptidase-4 inhibitors. Pharmacol Ther. 2016 Nov;167:100-107. doi: 10.1016/j.pharmthera.2016.07.009.
  • Connelly KA, Advani A, Zhang Y, et al. Dipeptidyl peptidase-4 inhibition improves cardiac function in experimental myocardial infarction: role of stromal cell-derived factor-1α. J Diabetes. 2016 Jan;8(1):63–75. doi: 10.1111/1753-0407.12258
  • Chung ES, Miller L, Patel AN, et al. Changes in ventricular remodelling and clinical status during the year following a single administration of stromal cell-derived factor-1 non-viral gene therapy in chronic ischaemic heart failure patients: the STOP-HF randomized Phase II trial. Eur Heart J. 2015 Sep 1;36(33):2228–2238.
  • Zarrouk-Mahjoub S, Zaghdoudi M, Amira Z, et al. Pro- and anti-inflammatory cytokines in post-infarction left ventricular remodeling. Int J Cardiol. 2016 Jul;5(221):632–636.
  • Frangogiannis NG. Interleukin-1 in cardiac injury, repair, and remodeling: pathophysiologic and translational concepts. Discoveries (Craiova). 2015 Jan-Mar;3(1). pii: e41.
  • Morton AC, Rothman AMK, Greenwood JP, et al. The effect of interleukin-1 receptor antagonist therapy on markers of inflammation in non-ST elevation acute coronary syndromes: the MRC-ILA Heart Study. Eur Heart J. 2015 Feb 7;36(6):377–384.
  • Abbate A, Kontos MC, Grizzard JD, et al. Interleukin-1 blockade with anakinra to prevent adverse cardiac remodeling after acute myocardial infarction (Virginia Commonwealth University Anakinra Remodeling Trial [VCU-ART] Pilot study). Am J Cardiol. 2010 May 15;105(10):1371–7.e1.
  • Abbate A, Van Tassell BW, Biondi-Zoccai G, et al. Effects of interleukin-1 blockade with anakinra on adverse cardiac remodeling and heart failure after acute myocardial infarction [from the Virginia Commonwealth University-Anakinra Remodeling Trial (2) (VCU-ART2) pilot study]. Am J Cardiol. 2013 May 15;111(10):1394–1400.
  • Sonnino C, Christopher S, Oddi C, et al. Leukocyte activity in patients with ST-segment elevation acute myocardial infarction treated with anakinra. Mol Med Camb Mass. 2014;20:486–489.
  • Abbate A, Kontos MC, Abouzaki NA, et al. Comparative safety of interleukin-1 blockade with anakinra in patients with ST-segment elevation acute myocardial infarction (from the VCU-ART and VCU-ART2 pilot studies). Am J Cardiol. 2015 Feb 1;115(3):288–292. doi: 10.1016/j.amjcard.2014.11.003.
  • Toldo S, Mezzaroma E, Bressi E, et al. Interleukin-1β blockade improves left ventricular systolic/diastolic function and restores contractility reserve in severe ischemic cardiomyopathy in the mouse. Journal of Cardiovascular Pharmacology. 2014 Jul;64(1):1–6.
  • Toldo S, Mezzaroma E, Van Tassell BW, et al. Interleukin-1β blockade improves cardiac remodelling after myocardial infarction without interrupting the inflammasome in the mouse. Exp Physiol. 2013 Mar;98(3):734–745.
  • Zeng Z, Yu K, Chen L, et al. interleukin-2/anti-interleukin-2 immune complex attenuates cardiac remodeling after myocardial infarction through expansion of regulatory t cells. J Immunol Res. 2016;2016:8493767.
  • Abeywardena MY, Leifert WR, Warnes KE, et al. Cardiovascular biology of interleukin-6. Curr Pharm Des. 2009;15(15):1809–1821.
  • Kleveland O, Kunszt G, Bratlie M, et al. Effect of a single dose of the interleukin-6 receptor antagonist tocilizumab on inflammation and troponin T release in patients with non-ST-elevation myocardial infarction: a double-blind, randomized, placebo-controlled phase 2 trial. Eur Heart J. 2016 Aug 7;37(30):2406–2413.
  • Fahim MR, Halim SM, Kamel I. Tumor necrosis factor alpha in patients with acute myocardial infarction. Egypt J Immunol Egypt Assoc Immunol. 2004;11(1):31–37.
  • Kehmeier ES, Lepper W, Kropp M, et al. TNF-α, myocardial perfusion and function in patients with ST-segment elevation myocardial infarction and primary percutaneous coronary intervention. Clin Res Cardiol Off J Ger Card Soc. 2012 Oct;101(10):815–827.
  • Padfield GJ, Din JN, Koushiappi E, et al. Cardiovascular effects of tumour necrosis factor α antagonism in patients with acute myocardial infarction: a first in human study. Heart Br Card Soc. 2013 Sep;99(18):1330–1335.
  • Venkatachalam K, Prabhu SD, Reddy VS, et al. Neutralization of interleukin-18 ameliorates ischemia/reperfusion-induced myocardial injury. J Biol Chem. 2009 Mar 20;284(12):7853–7865.
  • Tak PP, Bacchi M, Bertolino M. Pharmacokinetics of IL-18 binding protein in healthy volunteers and subjects with rheumatoid arthritis or plaque psoriasis. Eur J Drug Metab Pharmacokinet. 2006 Jun;31(2):109–116.
  • Shen B, Li J, Gao L, et al. Role of CC-chemokine receptor 5 on myocardial ischemia-reperfusion injury in rats. Mol Cell Biochem. 2013 Jun;378(1–2):137–144.
  • Zamilpa R, Kanakia R, Cigarroa J, et al. CC chemokine receptor 5 deletion impairs macrophage activation and induces adverse remodeling following myocardial infarction. Am J Physiol Heart Circ Physiol. 2011 Apr;300(4):H1418–26.
  • Dewald O, Zymek P, Winkelmann K, et al. CCL2/Monocyte Chemoattractant Protein-1 regulates inflammatory responses critical to healing myocardial infarcts. Circ Res. 2005 Apr 29;96(8):881–889.
  • Al-Amran FG, Manson MZ, Hanley TK, et al. Blockade of the monocyte chemoattractant protein-1 receptor pathway ameliorates myocardial injury in animal models of ischemia and reperfusion. Pharmacology. 2014;93(5–6):296–302.
  • Kaikita K, Hayasaki T, Okuma T, et al. Targeted deletion of CC chemokine receptor 2 attenuates left ventricular remodeling after experimental myocardial infarction. Am J Pathol. 2004 Aug;165(2):439–447.
  • Ferdinandy P, Danial H, Ambrus I, et al. Peroxynitrite is a major contributor to cytokine-induced myocardial contractile failure. Circ Res. 2000 Aug 4;87(3):241–247.
  • Suematsu N, Tsutsui H, Wen J, et al. Oxidative stress mediates tumor necrosis factor-alpha-induced mitochondrial DNA damage and dysfunction in cardiac myocytes. Circulation. 2003 Mar 18;107(10):1418–1423.
  • Hennekens CH, Buring JE, Manson JE, et al. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med. 1996 May 2;334(18):1145–1149.
  • Yusuf S, Dagenais G, Pogue J, et al. Vitamin E supplementation and cardiovascular events in high-risk patients. The heart outcomes prevention evaluation study investigators. N Engl J Med. 2000 Jan 20;342(3):154–160.
  • Fauconnier J, Meli AC, Thireau J, et al. Ryanodine receptor leak mediated by caspase-8 activation leads to left ventricular injury after myocardial ischemia-reperfusion. Proc Natl Acad Sci U S A. 2011 Aug 9;108(32):13258–13263.
  • Ago T, Kuroda J, Pain J, et al. Upregulation of Nox4 by hypertrophic stimuli promotes apoptosis and mitochondrial dysfunction in cardiac myocytes. Circ Res. 2010 Apr 16;106(7):1253–1264.
  • Matsushima S, Kuroda J, Zhai P, et al. Tyrosine kinase FYN negatively regulates NOX4 in cardiac remodeling. J Clin Invest. 2016 Sep 1;126(9):3403–3416.
  • Xiao J, She Q, Wang Y, et al. Effect of allopurinol on cardiomyocyte apoptosis in rats after myocardial infarction. Eur J Heart Fail. 2009 Jan;11(1):20–27.
  • Sagor MAT, Tabassum N, Potol MA, et al. xanthine oxidase inhibitor, allopurinol, prevented oxidative stress, fibrosis, and myocardial damage in isoproterenol induced aged rats. Oxid Med Cell Longev. 2015;2015:478039.
  • Wang S, Li Y, Song X, et al. Febuxostat pretreatment attenuates myocardial ischemia/reperfusion injury via mitochondrial apoptosis. J Transl Med. 2015;13:209.
  • Ekeløf S, Jensen SE, Rosenberg J, et al. Reduced oxidative stress in STEMI patients treated by primary percutaneous coronary intervention and with antioxidant therapy: a systematic review. Cardiovasc Drugs. Ther Spons Int Soc Cardiovasc Pharmacother. 2014 Apr;28(2):173–181.
  • Forrat R, Sebbag L, Ferrera R, et al. Effect of colchicine on circulating and myocardial neutrophils and on infarct size in a canine model of ischemia and reperfusion. J Cardiovasc Pharmacol. 1996 Jun;27(6):876–883.
  • Deftereos S, Giannopoulos G, Angelidis C, et al. Anti-inflammatory treatment with colchicine in acute myocardial infarction: a pilot study. Circulation. 2015 Oct 13;132(15):1395–1403.
  • Cronstein BN, Naime D, Ostad E. The antiinflammatory mechanism of methotrexate. Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation. J Clin Invest. 1993 Dec;92(6):2675–2682.
  • Riksen NP, Barrera P, Van Den Broek PHH, et al. Methotrexate modulates the kinetics of adenosine in humans in vivo. Ann Rheum Dis. 2006 Apr;65(4):465–470.
  • Asanuma H, Sanada S, Ogai A, et al. Methotrexate and MX-68, a new derivative of methotrexate, limit infarct size via adenosine-dependent mechanisms in canine hearts. J Cardiovasc Pharmacol. 2004 Apr;43(4):574–579.
  • Moreira DM, Lueneberg ME, Da Silva RL, et al. Rationale and design of the TETHYS trial: the effects of methotrexate therapy on myocardial infarction with ST-segment elevation. Cardiology. 2013;126(3):167–170.
  • Van Dijk RA, Rijs K, Wezel A, et al. Systematic evaluation of the cellular innate immune response during the process of human atherosclerosis. J Am Heart Assoc. 2016 Jun 1; cited 2016 Dec 4;5(6):e002860.
  • Mestas J, Hughes CCW, Mice O. Not men: differences between mouse and human immunology. J Immunol. 2004 Mar 1;172(5):2731–2738.
  • Mallat Z, Taleb S, Ait-Oufella H, et al. The role of adaptive T cell immunity in atherosclerosis. J Lipid Res. 2009 Apr;50(Suppl):S364–9.

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