title: Inflammatory mechanisms in myocardial infarction.
abstract: Myocardial infarction is associated with an inflammatory response, ultimately leading to healing and scar formation. Reperfused myocardial infarcts exhibit an enhanced inflammatory reaction, and are associated with improved cardiac repair and patient survival. This review summarizes our current knowledge of the inflammatory mechanisms mediating injury and repair following myocardial ischemia and reperfusion. Myocardial necrosis is associated with complement activation and free radical generation, triggering a cytokine cascade and chemokine upregulation. Interleukin (IL)-8 and C5a are released in the ischemic myocardium, and may have a crucial role in neutrophil recruitment. Extravasated neutrophils may induce potent cytotoxic effects through the release of proteolytic enzymes and the adhesion with Intercellular Adhesion Molecule (ICAM)-1 expressing cardiomyocytes. However, despite these potentially injurious effects, the post-reperfusion inflammatory response may significantly enhance healing. Monocyte Chemoattractant Protein (MCP)-1 is induced in the infarcted area and may regulate mononuclear cell recruitment. Accumulation of monocyte-derived macrophages, and mast cells may increase expression of growth factors inducing angiogenesis and fibroblast accumulation in the infarct. In addition, expression of cytokines inhibiting the inflammatory response, such as Interleukin (IL)-10 may suppress injury. Matrix Metalloproteinases (MMPs) and their inhibitors regulate extracellular matrix deposition and play an important role in mediating ventricular remodeling. Inflammatory mediators may induce recruitment of blood-derived primitive stem cells in the healing infarct, which may differentiate into endothelial cells and even lead to limited myocardial regeneration. Understanding the cellular and molecular steps involved in regulating infarct healing may lead to specific interventions aimed at optimizing cardiac repair.
authors.affiliation: Section of Cardiovascular Sciences, Department of Medicine, The Methodist Hospital, Houston TX, USA.
authors.forename: Guofeng
authors.initials: G
authors.lastname: Ren
authors.forename: Oliver
authors.initials: O
authors.lastname: Dewald
authors.forename: Nikolaos G
authors.initials: NG
authors.lastname: Frangogiannis
mesh_terms: D000818:Animals; D002921:Cicatrix / Q000473:pathology; D016207:Cytokines / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D018836:Inflammation Mediators / Q000502:physiology; D009203:Myocardial Infarction / Q000473:pathology*; D009206:Myocardium / Q000473:pathology*; D020556:Neutrophil Infiltration; D012038:Regeneration / Q000502:physiology; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators