Negative regulators of inflammation as endogenous protective mechanisms in postinfarction remodeling

Myocardial infarction triggers an intense inflammatory reaction that serves to clear the wound from dead cells and matrix debris while promoting cardiac repair and formation of a scar. Dysregulated inflammation following cardiac injury has adverse consequences on the reparative response enhancing dilative remodeling and causing contractile dysfunction. Inhibitory molecular signals and suppressive pathways that prevent excessive or uncontrolled inflammation are activated in the infarcted myocardium and may protect from the development of adverse remodeling. This chapter discusses the cellular effectors and molecular signals responsible for suppression and containment of the postinfarction inflammatory response. Neutrophils, monocytes/macrophages, and lymphocyte subpopulations with suppressive properties, dendritic cells, vascular cells, fibroblasts, and extracellular matrix proteins contribute to inhibition of the inflammatory signals by producing soluble suppressive mediators (such as transforming growth factor-ß, interleukin-10, and lipid-derived mediators) and through activation of intracellular inhibitory signals. We propose that dilative remodeling in patients with myocardial infarction may reflect impairment of suppressive anti-inflammatory pathways. Selective inhibition of inflammatory mediators in patient subpopulations with overactive postinfarction inflammation may protect from the development of heart failure.