Ž . International Immunopharmacology 1 2001 403–414 www.elsevier.comrlocaterintimp Review CRP, a major culprit in complement-mediated tissue damage in acute myocardial infarction? Remco Nijmeijer a,b,c,e, ) , Wim K. Lagrand a,c , Cees A. Visser a,c , Chris J.L.M. Meijer b , Hans W.M. Niessen a,b , C. Erik Hack a,d,e a ICaR-VU, UniÕersity Hospital A Vrije UniÕersiteit B , Amsterdam, Netherlands b Department of Pathology, UniÕersity Hospital A Vrije UniÕersiteit B , Amsterdam, Netherlands c Department of Cardiology, UniÕersity Hospital A Vrije UniÕersiteit B , Amsterdam, Netherlands d Department of Clinical Chemistry, UniÕersity Hospital A Vrije UniÕersiteit B , Amsterdam, Netherlands e Department of Pathophysiology of Plasma Proteins, CLB, Sanquin Blood Supply Foundation, Amsterdam, Netherlands Accepted 30 October 2000 Keywords: Complement; CRP; Acute myocardial infarction 1. Introduction Ž . Acute myocardial infarction AMI is one of the major causes of mortality and morbidity in the west- ern world. About 1.5 million individuals in the United States suffer an acute myocardial infarction annually, of which approximately 500,000 are hospitalized. Mortality is due to arrhythmia, cardiac rupture and acute heart failure, whereas morbidity often results AbbreÕiations: AMI, Acute myocardial infarction; C1-INH, C1 esterase inhibitor; CoVF, Cobra venom factor; CRP, C-reac- tive protein; CR1, Complement receptor 1; ICAM-1, Inter cellular adhesion molecule-1; MAC, Membrane attack complex; MBL, Ž Mannose binding lectin; PLA , Phospholipase A sPLA — 2 2 2 Secretory phospholipase A , cPLA —Cytosolic phospholipase 2 2 . A ; PMN, Polymorphonuclear granulocytes; PTCA, Percutane 2 transluminal coronary angioplasty; RCA, Regulator of comple- ment activation; rt-PA, recombinant tissue-type plasminogen acti- vator; SK, Streptokinase; UAP, Unstable angina pectoris ) Corresponding author. Department of Pathology, University Hospital AVrije UniversiteitB, Room Nr. PA002, De Boelelaan 1117, 1081 HV Amsterdam, P.O. Box 1007 MB, Netherlands. Tel.: q 31-20-444-4003; fax: q 31-20-444-2964. Ž . E-mail address: R.Nijmeijer@AZVU.NL R. Nijmeijer . from chronic heart failure. Classic acute myocardial infarction with extensive necrosis occurs when per- fusion of myocardium is reduced severely below its Ž . needs for an extended interval hours , causing pro- found, prolonged ischemia resulting in permanent loss of function through cell death by coagulation necrosis. In contrast, if restoration of myocardial blood flow follows after a short period of flow deprivation, loss of cell viability generally is limited. Reperfusion of ischemic myocardium therefore is necessary to salvage tissue from eventual death. Paradoxically, reperfusion after intermediate periods of ischemia is associated with pathologic changes that result in further expansion of the initiated tissue damage. In ischemiarreperfusion experiments in rabbits, Farb et al., for example, showed that a subset of myocytes in border areas of the ischemic region, viable at the beginning of reperfusion, subsequently wx progress to irreversible injury during reperfusion 1 . Cell death during reperfusion does not occur primar- ily via necrosis, but also results from apoptosis, via wx upregulation of caspase activity 2 . This ‘reperfu- sion injury’ of the myocardium shares many charac- 1567-5769r01r$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. Ž . PII: S1567-5769 00 00044-8