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Horm Metab Res 2008; 40(9): 626-634
DOI: 10.1055/s-0028-1083786
Review

© Georg Thieme Verlag KG Stuttgart · New York

Complement Activation and Cardiovascular Disease

M. Bjerre 1 , T. K. Hansen 1 , A. Flyvbjerg 1
  • 1The Medical Research Laboratories, Clinical Institute and Immunoendocrine Research Unit, Medical Department M (Diabetes and Endocrinology), Aarhus University Hospital, Aarhus C, Denmark
Further Information

Publication History

received 04.09.2007

accepted 14.11.2007

Publication Date:
15 September 2008 (online)

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Abstract

The mechanisms by which tissue injury after acute myocardial infarction occurs have not been fully elucidated, but considerable evidence suggests that activation of complement plays an important role in the pathophysiology. Reperfusion of the ischemic myocardium is strictly necessary to rescue the exposed tissue from eventual death. However, reversion of the blood supply is also associated with reperfusion injury contributing to tissue injury. Activation of the complement system has indisputable beneficial effects in the immune defense and in the clearance of damaged tissue and apoptotic cells, but excessive activation of the system may lead to uncontrolled tissue damage. This review focuses on the role of complement activation, with focus on the lectin pathway, endothelial dysfunction and cardiovascular diseases, including ischemic heart disease and diabetic angiopathy. Finally, potential therapeutic strategies targeting the complement system are discussed.

Key words

complement - inflammation - cardiovascular disease - ischemia - diabetes mellitus

References

  • 1 Rosamond W, Flegal K, Friday G, Furie K, Go A, Greenlund K, Haase N, Ho M, Howard V, Kissela B, Kittner S, Lloyd-Jones D, MacDermott M, Meigs J, Moy C, Nichol G, O’Donnell CJ, Roger V, Rumsfeld J, Sorlie P, Steinberger J, Thom T, Wasserthiel-Smoller S, Hong Y. Heart disease and stroke statistics – 2007 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee.  Circulation. 2007;  115 e69-e171
    CrossrefPubMedGoogle Scholar
  • 2 Cooper NR. The classical complement pathway: activation and regulation of the first complement component.  Adv Immunol. 1985;  37 151-216
    PubMedGoogle Scholar
  • 3 Muller-Eberhard HJ. Molecular organization and function of the complement system.  Annu Rev Biochem. 1988;  57 321-347
    CrossrefPubMedGoogle Scholar
  • 4 Matsushita M, Endo Y, Hamasaki N, Fujita T. Activation of the lectin complement pathway by ficolins.  Int Immunopharmacol. 2001;  1 359-363
    CrossrefPubMedGoogle Scholar
  • 5 Frederiksen PD, Thiel S, Larsen CB, Jensenius JC. M-ficolin, an innate immune defence molecule, binds patterns of acetyl groups and activates complement.  Scand J Immunol. 2005;  62 462-473
    CrossrefPubMedGoogle Scholar
  • 6 Holmskov U, Thiel S, Jensenius JC. Collectins and ficolins: humoral lectins of the innate immune defense.  Annu Rev Immunol. 2003;  21 547-578
    CrossrefPubMedGoogle Scholar
  • 7 Ikeda K, Sannoh T, Kawasaki N, Kawasaki T, Yamashina I. Serum lectin with known structure activates complement through the classical pathway.  J Biol Chem. 1987;  262 7451-7454
    PubMedGoogle Scholar
  • 8 Thiel S, Vorup-Jensen T, Stover CM, Schwaeble W, Laursen SB, Poulsen K, Willis AC, Eggleton P, Hansen S, Holmskov U, Reid KB, Jensenius JC. A second serine protease associated with mannan-binding lectin that activates complement.  Nature. 1997;  386 506-510
    CrossrefPubMedGoogle Scholar
  • 9 Holmskov U, Malhotra R, Sim RB, Jensenius JC. Collectins: collagenous C-type lectins of the innate immune defense system.  Immunol Today. 1994;  15 67-74
    CrossrefPubMedGoogle Scholar
  • 10 Steffensen R, Thiel S, Varming K, Jersild C, Jensenius JC. Detection of structural gene mutations and promoter polymorphisms in the mannan-binding lectin (MBL) gene by polymerase chain reaction with sequence-specific primers.  J Immunol Methods. 2000;  241 33-42
    CrossrefPubMedGoogle Scholar
  • 11 Super M, Thiel S, Lu J, Levinsky RJ, Turner MW. Association of low levels of mannan-binding protein with a common defect of opsonisation.  Lancet. 1989;  2 1236-1239
    PubMedGoogle Scholar
  • 12 Johnson E, Hetland G. Human umbilical vein endothelial cells synthesize functional C3, C5, C6, C8 and C9 in vitro.  Scand J Immunol. 1991;  33 667-671
    CrossrefPubMedGoogle Scholar
  • 13 Langeggen H, Pausa M, Johnson E, Casarsa C, Tedesco F. The endothelium is an extrahepatic site of synthesis of the seventh component of the complement system.  Clin Exp Immunol. 2000;  121 69-76
    CrossrefPubMedGoogle Scholar
  • 14 Langeggen H, Berge KE, Macor P, Fischetti F, Tedesco F, Hetland G, Berg K, Johnson E. Detection of mRNA for the terminal complement components C5, C6, C8 and C9 in human umbilical vein endothelial cells in vitro.  Apmis. 2001;  109 73-78
    CrossrefPubMedGoogle Scholar
  • 15 Niculescu F, Rus H. Mechanisms of signal transduction activated by sublytic assembly of terminal complement complexes on nucleated cells.  Immunol Res. 2001;  24 191-199
    CrossrefPubMedGoogle Scholar
  • 16 Tedesco F, Fischetti F, Pausa M, Dobrina A, Sim RB, Daha MR. Complement-endothelial cell interactions: pathophysiological implications.  Mol Immunol. 1999;  36 261-268
    CrossrefPubMedGoogle Scholar
  • 17 Ghebrehiwet B, Peerschke EI. cC1q-R (calreticulin) and gC1q-R/p33: ubiquitously expressed multi-ligand binding cellular proteins involved in inflammation and infection.  Mol Immunol. 2004;  41 173-183
    CrossrefPubMedGoogle Scholar
  • 18 Oroszlan M, Daha MR, Cervenak L, Prohaszka Z, Fust G, Roos A. MBL and C1q compete for interaction with human endothelial cells.  Mol Immunol. 2007;  44 1150-1158
    CrossrefPubMedGoogle Scholar
  • 19 Schmaier AH, Murray SC, Heda GD, Farber A, Kuo A, MacCrae K, Cines DB. Synthesis and expression of C1 inhibitor by human umbilical vein endothelial cells.  J Biol Chem. 1989;  264 18173-18179
    PubMedGoogle Scholar
  • 20 Gulati P, Guc D, Lemercier C, Lappin D, Whaley K. Expression of the components and regulatory proteins of the classical pathway of complement in normal and diseased synovium.  Rheumatol Int. 1994;  14 13-19
    CrossrefPubMedGoogle Scholar
  • 21 Schlaf G, Demberg T, Beisel N, Schieferdecker HL, Gotze O. Expression and regulation of complement factors H and I in rat and human cells: some critical notes.  Mol Immunol. 2001;  38 231-239
    CrossrefPubMedGoogle Scholar
  • 22 Berge V, Berge KE, Johnson E. Vitronectin modulates the expression of complement components of the terminal pathway synthesized by human umbilical vein endothelial cells in vitro.  Apmis. 1996;  104 523-530
    CrossrefPubMedGoogle Scholar
  • 23 Berge V, Johnson E, Hogasen K. Clusterin and the terminal complement pathway synthesized by human umbilical vein endothelial cells are closely linked when detected on co-cultured agarose beads.  APMIS. 1997;  105 17-24
    CrossrefPubMedGoogle Scholar
  • 24 Hoppe HC, Wet BJ de, Cywes C, Daffe M, Ehlers MR. Identification of phosphatidylinositol mannoside as a mycobacterial adhesin mediating both direct and opsonic binding to nonphagocytic mammalian cells.  Infect Immun. 1997;  65 3896-3905
    PubMedGoogle Scholar
  • 25 Drexler H. Endothelial dysfunction: clinical implications.  Prog Cardiovasc Dis. 1997;  39 287-324
    CrossrefPubMedGoogle Scholar
  • 26 Endemann DH, Schiffrin EL. Endothelial dysfunction.  J Am Soc Nephrol. 2004;  15 1983-1992
    CrossrefPubMedGoogle Scholar
  • 27 Esper RJ, Nordaby RA, Vilarino JO, Paragano A, Cacharron JL, Machado RA. Endothelial dysfunction: a comprehensive appraisal.  Cardiovasc Diabetol. 2006;  5 4
    CrossrefPubMedGoogle Scholar
  • 28 Kyrou I, Tsigos C. Stress mechanisms and metabolic complications.  Horm Metab Res. 2007;  39 430-438
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Bellin C, Wiza DH de, Wiernsperger NF, Rosen P. Generation of reactive oxygen species by endothelial and smooth muscle cells: influence of hyperglycemia and metformin.  Horm Metab Res. 2006;  38 732-739
    Article in Thieme ConnectPubMedGoogle Scholar
  • 30 Neunteufl T, Heher S, Katzenschlager R, Wolfl G, Kostner K, Maurer G, Weidinger F. Late prognostic value of flow-mediated dilation in the brachial artery of patients with chest pain.  Am J Cardiol. 2000;  86 207-210
    CrossrefPubMedGoogle Scholar
  • 31 Kostner KM, Fahti RB, Case C, Hobson P, Tate J, Marwick TH. Inflammation, complement activation and endothelial function in stable and unstable coronary artery disease.  Clin Chim Acta. 2006;  365 129-134
    CrossrefPubMedGoogle Scholar
  • 32 Czermak BJ, Sarma V, Bless NM, Schmal H, Friedl HP, Ward PA. In vitro and in vivo dependency of chemokine generation on C5a and TNF-alpha.  J Immunol. 1999;  162 2321-2325
    PubMedGoogle Scholar
  • 33 Collard CD, Montalto MC, Reenstra WR, Buras JA, Stahl GL. Endothelial oxidative stress activates the lectin complement pathway: role of cytokeratin 1.  Am J Pathol. 2001;  159 1045-1054
    PubMedGoogle Scholar
  • 34 Collard CD, Vakeva A, Morrissey MA, Agah A, Rollins SA, Reenstra WR, Buras JA, Meri S, Stahl GL. Complement activation after oxidative stress: role of the lectin complement pathway.  Am J Pathol. 2000;  156 1549-1556
    PubMedGoogle Scholar
  • 35 Mold C, Morris CA. Complement activation by apoptotic endothelial cells following hypoxia/reoxygenation.  Immunology. 2001;  102 359-364
    CrossrefPubMedGoogle Scholar
  • 36 Stahl GL, Reenstra WR, Frendl G. Complement-mediated loss of endothelium-dependent relaxation of porcine coronary arteries. Role of the terminal membrane attack complex.  Circ Res. 1995;  76 575-583
    PubMedGoogle Scholar
  • 37 Lennon PF, Collard CD, Morrissey MA, Stahl GL. Complement-induced endothelial dysfunction in rabbits: mechanisms, recovery, and gender differences.  Am J Physiol. 1996;  270 H1924-H1932
    PubMedGoogle Scholar
  • 38 Riedemann NC, Ward PA. Complement in ischemia reperfusion injury.  Am J Pathol. 2003;  162 363-367
    PubMedGoogle Scholar
  • 39 Arumugam TV, Shiels IA, Woodruff TM, Granger DN, Taylor SM. The role of the complement system in ischemia-reperfusion injury.  Shock. 2004;  21 401-409
    CrossrefPubMedGoogle Scholar
  • 40 Khalil AA, Aziz FA, Hall JC. Reperfusion injury.  Plast Reconstr Surg. 2006;  117 1024-1033
    CrossrefPubMedGoogle Scholar
  • 41 Yasuda M, Takeuchi K, Hiruma M, Iida H, Tahara A, Itagane H, Toda I, Akioka K, Teragaki M, Oku H. et al . The complement system in ischemic heart disease.  Circulation. 1990;  81 156-163
    PubMedGoogle Scholar
  • 42 Lagrand WK, Niessen HW, Wolbink GJ, Jaspars LH, Visser CA, Verheugt FW, Meijer CJ, Hack CE. C-reactive protein colocalizes with complement in human hearts during acute myocardial infarction.  Circulation. 1997;  95 97-103
    PubMedGoogle Scholar
  • 43 Iltumur K, Karabulut A, Toprak G, Toprak N. Complement activation in acute coronary syndromes.  APMIS. 2005;  113 167-174
    CrossrefPubMedGoogle Scholar
  • 44 Muscari A, Massarelli G, Bastagli L, Poggiopollini G, Tomassetti V, Drago G, Martignani C, Pacilli P, Boni P, Puddu P. Relationship of serum C3 to fasting insulin, risk factors and previous ischaemic events in middle-aged men.  Eur Heart J. 2000;  21 1081-1090
    CrossrefPubMedGoogle Scholar
  • 45 Szeplaki G, Prohaszka Z, Duba J, Rugonfalvi-Kiss S, Karadi I, Kokai M, Kramer J, Fust G, Kleiber M, Romics L, Varga L. Association of high serum concentration of the third component of complement (C3) with pre-existing severe coronary artery disease and new vascular events in women.  Atherosclerosis. 2004;  177 383-389
    CrossrefPubMedGoogle Scholar
  • 46 Palikhe A, Sinisalo J, Seppanen M, Haario H, Meri S, Valtonen V, Nieminen MS, Lokki ML. Serum complement C3/C4 ratio, a novel marker for recurrent cardiovascular events.  Am J Cardiol. 2007;  99 890-895
    CrossrefPubMedGoogle Scholar
  • 47 Engstrom G, Hedblad B, Janzon L, Lindgarde F. Complement C3 and C4 in plasma and incidence of myocardial infarction and stroke: a population-based cohort study.  Eur J Cardiovasc Prev Rehabil. 2007;  14 392-397
    CrossrefPubMedGoogle Scholar
  • 48 Best LG, Davidson M, North KE, MacCluer JW, Zhang Y, Lee ET, Howard BV, DeCroo S, Ferrell RE. Prospective analysis of mannose-binding lectin genotypes and coronary artery disease in American Indians: the Strong Heart Study.  Circulation. 2004;  109 471-475
    CrossrefPubMedGoogle Scholar
  • 49 Saevarsdottir S, Oskarsson OO, Aspelund T, Eiriksdottir G, Vikingsdottir T, Gudnason V, Valdimarsson H. Mannan binding lectin as an adjunct to risk assessment for myocardial infarction in individuals with enhanced risk.  J Exp Med. 2005;  201 117-125
    CrossrefPubMedGoogle Scholar
  • 50 Norwood MG, Sayers RD, Roscher S, Lynch NJ, Sutton AJ, Schwaeble WJ. Consumption of mannan-binding lectin during abdominal aortic aneurysm repair.  Eur J Vasc Endovasc Surg. 2006;  31 239-243
    CrossrefPubMedGoogle Scholar
  • 51 Ueland T, Espevik T, Kjekshus J, Gullestad L, Omland T, Squire IB, Froland SS, Mollnes TE, Dickstein K, Aukrust P. Mannose binding lectin and soluble Toll-like receptor 2 in heart failure following acute myocardial infarction.  J Card Fail. 2006;  12 659-663
    CrossrefPubMedGoogle Scholar
  • 52 Biezeveld MH, Geissler J, Weverling GJ, Kuipers IM, Lam J, Ottenkamp J, Kuijpers TW. Polymorphisms in the mannose-binding lectin gene as determinants of age-defined risk of coronary artery lesions in Kawasaki disease.  Arthritis Rheum. 2006;  54 369-376
    CrossrefPubMedGoogle Scholar
  • 53 Schafranski MD, Stier A, Nisihara R, Messias-Reason IJ. Significantly increased levels of mannose-binding lectin (MBL) in rheumatic heart disease: a beneficial role for MBL deficiency.  Clin Exp Immunol. 2004;  138 521-525
    CrossrefPubMedGoogle Scholar
  • 54 Hill JH, Ward PA. The phlogistic role of C3 leukotactic fragments in myocardial infarcts of rats.  J Exp Med. 1971;  133 885-900
    CrossrefPubMedGoogle Scholar
  • 55 Pinckard RN, O’Rourke RA, Crawford MH, Grover FS, MacManus LM, Ghidoni JJ, Storrs SB, Olson MS. Complement localization and mediation of ischemic injury in baboon myocardium.  J Clin Invest. 1980;  66 1050-1056
    CrossrefPubMedGoogle Scholar
  • 56 MacManus LM, Kolb WP, Crawford MH, O’Rourke RA, Grover FL, Pinckard RN. Complement localization in ischemic baboon myocardium.  Lab Invest. 1983;  48 436-447
    PubMedGoogle Scholar
  • 57 Yasojima K, Kilgore KS, Washington RA, Lucchesi BR, MacGeer PL. Complement gene expression by rabbit heart: upregulation by ischemia and reperfusion.  Circ Res. 1998;  82 1224-1230
    PubMedGoogle Scholar
  • 58 Ito W, Schafer HJ, Bhakdi S, Klask R, Hansen S, Schaarschmidt S, Schofer J, Hugo F, Hamdoch T, Mathey D. Influence of the terminal complement-complex on reperfusion injury, no-reflow and arrhythmias: a comparison between C6-competent and C6-deficient rabbits.  Cardiovasc Res. 1996;  32 294-305
    CrossrefPubMedGoogle Scholar
  • 59 Vakeva A, Morgan BP, Tikkanen I, Helin K, Laurila P, Meri S. Time course of complement activation and inhibitor expression after ischemic injury of rat myocardium.  Am J Pathol. 1994;  144 1357-1368
    PubMedGoogle Scholar
  • 60 Vries B de, Walter SJ, Peutz-Kootstra CJ, Wolfs TG, Heurn LW van, Buurman WA. The mannose-binding lectin-pathway is involved in complement activation in the course of renal ischemia-reperfusion injury.  Am J Pathol. 2004;  165 1677-1688
    PubMedGoogle Scholar
  • 61 Walsh MC, Bourcier T, Takahashi K, Shi L, Busche MN, Rother RP, Solomon SD, Ezekowitz RA, Stahl GL. Mannose-binding lectin is a regulator of inflammation that accompanies myocardial ischemia and reperfusion injury.  J Immunol. 2005;  175 541-546
    PubMedGoogle Scholar
  • 62 Moller-Kristensen M, Wang W, Ruseva M, Thiel S, Nielsen S, Takahashi K, Shi L, Ezekowitz A, Jensenius JC, Gadjeva M. Mannan-binding lectin recognizes structures on ischaemic reperfused mouse kidneys and is implicated in tissue injury.  Scand J Immunol. 2005;  61 426-434
    CrossrefPubMedGoogle Scholar
  • 63 Crawford MH, Grover FL, Kolb WP, MacMahan CA, O’Rourke RA, MacManus LM, Pinckard RN. Complement and neutrophil activation in the pathogenesis of ischemic myocardial injury.  Circulation. 1988;  78 1449-1458
    PubMedGoogle Scholar
  • 64 Griselli M, Herbert J, Hutchinson WL, Taylor KM, Sohail M, Krausz T, Pepys MB. C-reactive protein and complement are important mediators of tissue damage in acute myocardial infarction.  J Exp Med. 1999;  190 1733-1740
    CrossrefPubMedGoogle Scholar
  • 65 Pepys MB, Hirschfield GM, Tennent GA, Gallimore JR, Kahan MC, Bellotti V, Hawkins PN, Myers RM, Smith MD, Polara A, Cobb AJ, Ley SV, Aquilina JA, Robinson CV, Sharif I, Gray GA, Sabin CA, Jenvey MC, Kolstoe SE, Thompson D, Wood SP. Targeting C-reactive protein for the treatment of cardiovascular disease.  Nature. 2006;  440 1217-1221
    CrossrefPubMedGoogle Scholar
  • 66 Niculescu F, Niculescu T, Rus H. C5b-9 terminal complement complex assembly on apoptotic cells in human arterial wall with atherosclerosis.  Exp Mol Pathol. 2004;  76 17-23
    CrossrefPubMedGoogle Scholar
  • 67 Rugonfalvi-Kiss S, Dosa E, Madsen HO, Endresz V, Prohaszka Z, Laki J, Karadi I, Gonczol E, Selmeci L, Romics L, Fust G, Entz L, Garred P. High rate of early restenosis after carotid eversion endarterectomy in homozygous carriers of the normal mannose-binding lectin genotype.  Stroke. 2005;  36 944-948
    CrossrefPubMedGoogle Scholar
  • 68 Szeplaki G, Varga L, Laki J, Dosa E, Madsen HO, Prohaszka Z, Szabo A, Acsady G, Selmeci L, Garred P, Fust G, Entz L. Elevated complement C3 is associated with early restenosis after eversion carotid endarterectomy.  Thromb Haemost. 2006;  96 529-534
    PubMedGoogle Scholar
  • 69 Fiane AE, Videm V, Lingaas PS, Heggelund L, Nielsen EW, Geiran OR, Fung M, Mollnes TE. Mechanism of complement activation and its role in the inflammatory response after thoracoabdominal aortic aneurysm repair.  Circulation. 2003;  108 849-856
    CrossrefPubMedGoogle Scholar
  • 70 Marshall SM, Flyvbjerg A. Prevention and early detection of vascular complications of diabetes.  BMJ. 2006;  333 475-480
    CrossrefPubMedGoogle Scholar
  • 71 Ryden L, Standl E, Bartnik M, Berghe G Van den, Betteridge J, Boer MJ de, Cosentino F, Jonsson B, Laakso M, Malmberg K, Priori S, Ostergren J, Tuomilehto J, Thrainsdottir I, Vanhorebeek I, Stramba-Badiale M, Lindgren P, Qiao Q, Priori SG, Blanc JJ, Budaj A, Camm J, Dean V, Deckers J, Dickstein K, Lekakis J, MacGregor K, Metra M, Morais J, Osterspey A, Tamargo J, Zamorano JL, Deckers JW, Bertrand M, Charbonnel B, Erdmann E, Ferrannini E, Flyvbjerg A, Gohlke H, Juanatey JR, Graham I, Monteiro PF, Parhofer K, Pyorala K, Raz I, Schernthaner G, Volpe M, Wood D. Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD).  Eur Heart J. 2007;  28 88-136
    CrossrefPubMedGoogle Scholar
  • 72 Hansen HH, Joensen AM, Riahi S, Malczynski J, Molenberg D, Ravkilde J. Short and long-term outcome in diabetic patients with acute myocardial infarction in the invasive era.  Scand Cardiovasc J. 2007;  41 19-24
    CrossrefPubMedGoogle Scholar
  • 73 Hansen TK, Tarnow L, Thiel S, Steffensen R, Stehouwer CD, Schalkwijk CG, Parving HH, Flyvbjerg A. Association between mannose-binding lectin and vascular complications in type 1 diabetes.  Diabetes. 2004;  53 1570-1576
    CrossrefPubMedGoogle Scholar
  • 74 Hansen TK, Gall MA, Tarnow L, Thiel S, Stehouwer CD, Schalkwijk CG, Parving HH, Flyvbjerg A. Mannose-binding lectin and mortality in type 2 diabetes.  Arch Intern Med. 2006;  166 2007-2013
    CrossrefPubMedGoogle Scholar
  • 75 Qin X, Goldfine A, Krumrei N, Grubissich L, Acosta J, Chorev M, Hays AP, Halperin JA. Glycation inactivation of the complement regulatory protein CD59: a possible role in the pathogenesis of the vascular complications of human diabetes.  Diabetes. 2004;  53 2653-2661
    CrossrefPubMedGoogle Scholar
  • 76 Hansen TK. Mannose-binding lectin (MBL) and vascular complications in diabetes.  Horm Metab Res. 2005;  37 ((Suppl 1)) 95-98
    Article in Thieme ConnectPubMedGoogle Scholar
  • 77 Hansen TK, Thiel S, Knudsen ST, Gravholt CH, Christiansen JS, Mogensen CE, Poulsen PL. Elevated levels of mannan-binding lectin in patients with type 1 diabetes.  J Clin Endocrinol Metab. 2003;  88 4857-4861
    CrossrefPubMedGoogle Scholar
  • 78 Saraheimo M, Forsblom C, Hansen TK, Teppo AM, Fagerudd J, Pettersson-Fernholm K, Thiel S, Tarnow L, Ebeling P, Flyvbjerg A, Groop PH. Increased levels of mannan-binding lectin in type 1 diabetic patients with incipient and overt nephropathy.  Diabetologia. 2005;  48 198-202
    CrossrefPubMedGoogle Scholar
  • 79 Hansen TK, Tarnow L, AS A, Thiel S, Parving HH, Flyvbjerg A. Mannose-binding lectin genotype and serum concentrations predict mortality in type 1 diabetes. In 66th Scientific session of the American Diabetes Organisation. Washington, USA 2006
  • 80 Hovind P, Hansen TK, Tarnow L, Thiel S, Steffensen R, Flyvbjerg A, Parving HH. Mannose-binding lectin as a predictor of microalbuminuria in type 1 diabetes: an inception cohort study.  Diabetes. 2005;  54 1523-1527
    CrossrefPubMedGoogle Scholar
  • 81 Ostergaard J, Thiel S, Gadjeva M, Hansen TK, Rasch R, Flyvbjerg A. Mannose-binding lectin deficiency attenuates renal changes in a streptozotocin-induced model of type 1 diabetes in mice.  Diabetologia. 2007;  50 1541-1549
    CrossrefPubMedGoogle Scholar
  • 82 Cannon 3rd RO. Mechanisms, management and future directions for reperfusion injury after acute myocardial infarction.  Nat Clin Pract Cardiovasc Med. 2005;  2 88-94
    CrossrefPubMedGoogle Scholar
  • 83 Vakeva AP, Agah A, Rollins SA, Matis LA, Li L, Stahl GL. Myocardial infarction and apoptosis after myocardial ischemia and reperfusion: role of the terminal complement components and inhibition by anti-C5 therapy.  Circulation. 1998;  97 2259-2267
    PubMedGoogle Scholar
  • 84 Amsterdam EA, Stahl GL, Pan HL, Rendig SV, Fletcher MP, Longhurst JC. Limitation of reperfusion injury by a monoclonal antibody to C5a during myocardial infarction in pigs.  Am J Physiol. 1995;  268 H448-H457
    PubMedGoogle Scholar
  • 85 Mahaffey KW, Granger CB, Nicolau JC, Ruzyllo W, Weaver WD, Theroux P, Hochman JS, Filloon TG, Mojcik CF, Todaro TG, Armstrong PW. Effect of pexelizumab, an anti-C5 complement antibody, as adjunctive therapy to fibrinolysis in acute myocardial infarction: the COMPlement inhibition in myocardial infarction treated with thromboLYtics (COMPLY) trial.  Circulation. 2003;  108 1176-1183
    CrossrefPubMedGoogle Scholar
  • 86 Granger CB, Mahaffey KW, Weaver WD, Theroux P, Hochman JS, Filloon TG, Rollins S, Todaro TG, Nicolau JC, Ruzyllo W, Armstrong PW. Pexelizumab, an anti-C5 complement antibody, as adjunctive therapy to primary percutaneous coronary intervention in acute myocardial infarction: the COMplement inhibition in Myocardial infarction treated with Angioplasty (COMMA) trial.  Circulation. 2003;  108 1184-1190
    CrossrefPubMedGoogle Scholar
  • 87 Theroux P, Armstrong PW, Mahaffey KW, Hochman JS, Malloy KJ, Rollins S, Nicolau JC, Lavoie J, Luong TM, Burchenal J, Granger CB. Prognostic significance of blood markers of inflammation in patients with ST-segment elevation myocardial infarction undergoing primary angioplasty and effects of pexelizumab, a C5 inhibitor: a substudy of the COMMA trial.  Eur Heart J. 2005;  26 1964-1970
    CrossrefPubMedGoogle Scholar
  • 88 Shernan SK, Fitch JC, Nussmeier NA, Chen JC, Rollins SA, Mojcik CF, Malloy KJ, Todaro TG, Filloon T, Boyce SW, Gangahar DM, Goldberg M, Saidman LJ, Mangano DT. Impact of pexelizumab, an anti-C5 complement antibody, on total mortality and adverse cardiovascular outcomes in cardiac surgical patients undergoing cardiopulmonary bypass.  Ann Thorac Surg. 2004;  77 942-949 , discussion 949–950
    CrossrefPubMedGoogle Scholar
  • 89 Mathew JP, Shernan SK, White WD, Fitch JC, Chen JC, Bell L, Newman MF. Preliminary report of the effects of complement suppression with pexelizumab on neurocognitive decline after coronary artery bypass graft surgery.  Stroke. 2004;  35 2335-2339
    CrossrefPubMedGoogle Scholar
  • 90 Verrier ED, Shernan SK, Taylor KM, Werf F Van de, Newman MF, Chen JC, Carrier M, Haverich A, Malloy KJ, Adams PX, Todaro TG, Mojcik CF, Rollins SA, Levy JH. Terminal complement blockade with pexelizumab during coronary artery bypass graft surgery requiring cardiopulmonary bypass: a randomized trial.  Jama. 2004;  291 2319-2327
    CrossrefPubMedGoogle Scholar
  • 91 Haverich A, Shernan SK, Levy JH, Chen JC, Carrier M, Taylor KM, Werf F Van de, Newman MF, Adams PX, Todaro TG, Laan M van der, Verrier ED. Pexelizumab reduces death and myocardial infarction in higher risk cardiac surgical patients.  Ann Thorac Surg. 2006;  82 486-492
    CrossrefPubMedGoogle Scholar
  • 92 Carrier M, Menasche P, Levy JH, Newman MF, Taylor KM, Haverich A, Chen JC, Shernan SK, Werf F Van de, Laan M van der, Todaro TG, Adams PX, Verrier ED. Inhibition of complement activation by pexelizumab reduces death in patients undergoing combined aortic valve replacement and coronary artery bypass surgery.  J Thorac Cardiovasc Surg. 2006;  131 352-356
    CrossrefPubMedGoogle Scholar
  • 93 Armstrong PW, Adams PX, Al-Khalidi HR, Hamm C, Holmes D, O'Neill W, Todaro TG, Vahanian A, Werf F Van de, Granger CB. Assessment of Pexelizumab in Acute Myocardial Infarction (APEX AMI): a multicenter, randomized, double-blind, parallel-group, placebo-controlled study of pexelizumab in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention.  Am Heart J. 2005;  149 402-407
    CrossrefPubMedGoogle Scholar
  • 94 Armstrong PW, Granger CB, Adams PX, Hamm C, Holmes  Jr  D, O'Neill WW, Todaro TG, Vahanian A, Werf F Van de. Pexelizumab for acute ST-elevation myocardial infarction in patients undergoing primary percutaneous coronary intervention: a randomized controlled trial.  JAMA. 2007;  297 43-51
    CrossrefPubMedGoogle Scholar
  • 95 Zhang H, Qin G, Liang G, Li J, Barrington RA, Liu DX. C5aR-mediated myocardial ischemia/reperfusion injury.  Biochem Biophys Res Commun. 2007;  357 446-452
    CrossrefPubMedGoogle Scholar
  • 96 Cicardi M, Zingale L, Zanichelli A, Pappalardo E, Cicardi B. C1 inhibitor: molecular and clinical aspects.  Springer Semin Immunopathol. 2005;  27 286-298
    CrossrefPubMedGoogle Scholar
  • 97 Asghar SS, Pasch MC. Therapeutic inhibition of the complement system. Y2K update.  Front Biosci. 2000;  5 E63-E81
    CrossrefPubMedGoogle Scholar
  • 98 Kirschfink M, Mollnes TE. C1-inhibitor: an anti-inflammatory reagent with therapeutic potential.  Expert Opin Pharmacother. 2001;  2 1073-1083
    CrossrefPubMedGoogle Scholar
  • 99 Inderbitzin D, Beldi G, Avital I, Vinci G, Candinas D. Local and remote ischemia-reperfusion injury is mitigated in mice overexpressing human C1 inhibitor.  Eur Surg Res. 2004;  36 142-147
    CrossrefPubMedGoogle Scholar
  • 100 Simoni MG De, Rossi E, Storini C, Pizzimenti S, Echart C, Bergamaschini L. The powerful neuroprotective action of C1-inhibitor on brain ischemia-reperfusion injury does not require C1q.  Am J Pathol. 2004;  164 1857-1863
    PubMedGoogle Scholar
  • 101 Bauernschmitt R, Bohrer H, Hagl S. Rescue therapy with C1-esterase inhibitor concentrate after emergency coronary surgery for failed PTCA.  Intensive Care Med. 1998;  24 635-638
    CrossrefPubMedGoogle Scholar
  • 102 Tassani P, Kunkel R, Richter JA, Oechsler H, Lorenz HP, Braun SL, Eising GP, Haas F, Paek SU, Bauernschmitt R, Jochum M, Lange R. Effect of C1-esterase-inhibitor on capillary leak and inflammatory response syndrome during arterial switch operations in neonates.  J Cardiothorac Vasc Anesth. 2001;  15 469-473
    CrossrefPubMedGoogle Scholar
  • 103 Zwaan C de, Kleine AH, Diris JH, Glatz JF, Wellens HJ, Strengers PF, Tissing M, Hack CE, Dieijen-Visser MP van, Hermens WT. Continuous 48-h C1-inhibitor treatment, following reperfusion therapy, in patients with acute myocardial infarction.  Eur Heart J. 2002;  23 1670-1677
    PubMedGoogle Scholar
  • 104 Fattouch K, Bianco G, Speziale G, Sampognaro R, Lavalle C, Guccione F, Dioguardi P, Ruvolo G. Beneficial effects of C1 esterase inhibitor in ST-elevation myocardial infarction in patients who underwent surgical reperfusion: a randomised double-blind study.  Eur J Cardiothorac Surg. 2007;  32 326-332
    CrossrefPubMedGoogle Scholar
  • 105 Weisman HF, Bartow T, Leppo MK, Marsh  Jr  HC, Carson GR, Concino MF, Boyle MP, Roux KH, Weisfeldt ML, Fearon DT. Soluble human complement receptor type 1: in vivo inhibitor of complement suppressing post-ischemic myocardial inflammation and necrosis.  Science. 1990;  249 146-151
    CrossrefPubMedGoogle Scholar
  • 106 Chavez-Cartaya RE, DeSola GP, Wright L, Jamieson NV, White DJ. Regulation of the complement cascade by soluble complement receptor type 1. Protective effect in experimental liver ischemia and reperfusion.  Transplantation. 1995;  59 1047-1052
    CrossrefPubMedGoogle Scholar
  • 107 Weiser MR, Williams JP, Moore  Jr  FD, Kobzik L, Ma M, Hechtman HB, Carroll MC. Reperfusion injury of ischemic skeletal muscle is mediated by natural antibody and complement.  J Exp Med. 1996;  183 2343-2348
    CrossrefPubMedGoogle Scholar
  • 108 Gillinov AM, DeValeria PA, Winkelstein JA, Wilson I, Curtis WE, Shaw D, Yeh CG, Rudolph AR, Baumgartner WA, Herskowitz A. et al . Complement inhibition with soluble complement receptor type 1 in cardiopulmonary bypass.  Ann Thorac Surg. 1993;  55 619-624
    PubMedGoogle Scholar
  • 109 Lazar HL, Bao Y, Gaudiani J, Rivers S, Marsh H. Total complement inhibition: an effective strategy to limit ischemic injury during coronary revascularization on cardiopulmonary bypass.  Circulation. 1999;  100 1438-1442
    PubMedGoogle Scholar
  • 110 Austen  Jr  WG, Kyriakides C, Favuzza J, Wang Y, Kobzik L, Moore  Jr  FD, Hechtman HB. Intestinal ischemia-reperfusion injury is mediated by the membrane attack complex.  Surgery. 1999;  126 343-348
    CrossrefPubMedGoogle Scholar
  • 111 Lazar HL, Bokesch PM, Lenta F van, Fitzgerald C, Emmett C, Marsh  Jr  HC, Ryan U. Soluble human complement receptor 1 limits ischemic damage in cardiac surgery patients at high risk requiring cardiopulmonary bypass.  Circulation. 2004;  110 II274-II279
    PubMedGoogle Scholar
  • 112 Lazar HL, Keilani T, Fitzgerald CA, Shapira OM, Hunter CT, Shemin RJ, Marsh  Jr  HC, Ryan US. Beneficial effects of complement inhibition with soluble complement receptor 1 (TP10) during cardiac surgery: is there a gender difference?.  Circulation. 2007;  116 I83-I88
    PubMedGoogle Scholar
  • 113 Li JS, Sanders SP, Perry AE, Stinnett SS, Jaggers J, Bokesch P, Reynolds L, Nassar R, Anderson PA. Pharmacokinetics and safety of TP10, soluble complement receptor 1, in infants undergoing cardiopulmonary bypass.  Am Heart J. 2004;  147 173-180
    CrossrefPubMedGoogle Scholar
  • 114 Zacharowski K, Otto M, Hafner G, Marsh  Jr  HC, Thiemermann C. Reduction of myocardial infarct size with sCR1sLe(x), an alternatively glycosylated form of human soluble complement receptor type 1 (sCR1), possessing sialyl Lewis x.  Br J Pharmacol. 1999;  128 945-952
    CrossrefPubMedGoogle Scholar
  • 115 Huang J, Kim LJ, Mealey R, Marsh  Jr  HC, Zhang Y, Tenner AJ, Connolly  Jr  ES, Pinsky DJ. Neuronal protection in stroke by an sLex-glycosylated complement inhibitory protein.  Science. 1999;  285 595-599
    CrossrefPubMedGoogle Scholar
  • 116 Souza DG, Esser D, Bradford R, Vieira AT, Teixeira MM. APT070 (Mirococept), a membrane-localised complement inhibitor, inhibits inflammatory responses that follow intestinal ischaemia and reperfusion injury.  Br J Pharmacol. 2005;  145 1027-1034
    CrossrefPubMedGoogle Scholar

Correspondence

M. BjerrePhD 

The Medical Research Laboratories

Clinical Institute and Immunoendocrine Research Unit

Medical Department M (Diabetes and Endocrinology)

Aarhus University Hospital

8000 Aarhus

Denmark

Phone: +45/8949/21 54

Fax: +45/8949/21 50

Email: mette.bjerre@ki.au.dk

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