title: The innate immune response in reperfused myocardium.
abstract: One of the major therapeutic challenges in the arena of interventional cardiology is to design strategies aimed at reducing myocardial tissue damage after myocardial infarction. In response to tissue injury, an innate immune response is initiated that orchestrates homeostatic responses and is a prerequisite for subsequent wound healing. An exaggerated inflammatory reaction, however, countervenes these beneficial effects and contributes to maladaptive tissue damage. Herein, we discuss the pathways involving the innate immune system that have been investigated in the setting of myocardial ischaemia and reperfusion injury. Endogenous 'danger' signals [danger-associated molecular patterns (DAMPs)] are expressed following tissue injury and alert the innate immune system. Toll-like receptors and the complement system are activated, resulting in an inflammatory reaction involving inflammatory cell influx and the production and release of inflammatory cytokines. A potential involvement of cell-derived microparticles in the modulation of the innate immune response following myocardial injury will also be discussed. Our future challenge lies within the counteraction of maladaptive inflammatory cascades, without interfering in the benign wound healing response, and in translating these anti-inflammatory strategies into clinical practice.
authors.affiliation: Department of Cardiology, University Medical Centre Utrecht, Utrecht, The Netherlands. l.timmers@umcutrecht.nl
authors.forename: Leo
authors.initials: L
authors.lastname: Timmers
authors.forename: Gerard
authors.initials: G
authors.lastname: Pasterkamp
authors.forename: Vince C
authors.initials: VC
authors.lastname: de Hoog
authors.forename: Fatih
authors.initials: F
authors.lastname: Arslan
authors.forename: Yolande
authors.initials: Y
authors.lastname: Appelman
authors.forename: Dominique P V
authors.initials: DP
authors.lastname: de Kleijn
mesh_terms: D055252:Cell-Derived Microparticles; D003165:Complement System Proteins / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation; D018836:Inflammation Mediators / Q000502:physiology; D009203:Myocardial Infarction / Q000276:immunology*; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000276:immunology*; D009206:Myocardium / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000276:immunology* / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D051193:Toll-Like Receptors; D003165:Complement System Proteins