title: Danger signals in the initiation of the inflammatory response after myocardial infarction.
abstract: During myocardial infarction, sterile inflammation occurs. The danger model is a solid theoretic framework that explains this inflammation as danger associated molecular patterns activate the immune system. The innate immune system can sense danger signals through different pathogen recognition receptors (PRR) such as toll-like receptors, nod-like receptors and receptors for advanced glycation endproducts. Activation of a PRR results in the production of cytokines and the recruitment of leukocytes to the site of injury. Due to tissue damage and necrosis of cardiac cells, danger signals such as extracellular matrix (ECM) breakdown products, mitochondrial DNA, heat shock proteins and high mobility box 1 are released. Matricellular proteins are non-structural proteins expressed in the ECM and are upregulated upon injury. Some members of the matricellular protein family (like tenascin-C, osteopontin, CCN1 and the galectins) have been implicated in the inflammatory and reparative responses following myocardial infarction and may function as danger signals. In a clinical setting, danger signals can function as prognostic and/or diagnostic biomarkers and for drug targeting. In this review we will provide an overview of the established knowledge on the role of danger signals in myocardial infarction and we will discuss areas of interest for future research.
authors.affiliation: Experimental Cardiology Laboratory, University Medical Center Utrecht, Heidelberglaan 100, Room G02.523, 3584 CX Utrecht, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: de Haan
authors.affiliation: Experimental Cardiology Laboratory, University Medical Center Utrecht, Heidelberglaan 100, Room G02.523, 3584 CX Utrecht, The Netherlands.
authors.forename: M B
authors.initials: MB
authors.lastname: Smeets
authors.affiliation: Experimental Cardiology Laboratory, University Medical Center Utrecht, Heidelberglaan 100, Room G02.523, 3584 CX Utrecht, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Pasterkamp
authors.affiliation: Experimental Cardiology Laboratory, University Medical Center Utrecht, Heidelberglaan 100, Room G02.523, 3584 CX Utrecht, The Netherlands.
authors.forename: F
authors.initials: F
authors.lastname: Arslan
mesh_terms: D000818:Animals; D004272:DNA, Mitochondrial / Q000502:physiology; D005353:Fibronectins / Q000502:physiology; D037483:Galectin 1 / Q000502:physiology; D024243:HMGB1 Protein / Q000502:physiology; D006360:Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000209:etiology*; D009203:Myocardial Infarction / Q000150:complications*; D053474:Nod1 Signaling Adaptor Protein / Q000502:physiology; D053495:Osteopontin / Q000502:physiology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000502:physiology; D051193:Toll-Like Receptors / Q000502:physiology
chemical_list: D004272:DNA, Mitochondrial; D005353:Fibronectins; D037483:Galectin 1; D024243:HMGB1 Protein; D006360:Heat-Shock Proteins; C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors; D053495:Osteopontin