The adult mammalian heart has negligible regenerative capacity; thus, sudden death of a large number of cardiomyocytes in the infarcted myocardium leads to replacement of dead cells with collagen-based scar. Repair of the infarcted heart can be divided into three distinct, but overlapping phases: the inflammatory phase, the proliferative phase and the maturation phase. Cardiomyocyte necrosis and matrix fragmentation in the infarcted myocardium release damage-associated molecular patterns (DAMPs) that activate innate immune cascades and trigger the inflammatory reaction. Induction of chemokines and cytokines is a hallmark of the post-infarction inflammatory response mediating recruitment of neutrophils and mononuclear cells in the myocardium. As infiltrating leukocytes clear the wound from dead cells and matrix debris, pro-inflammatorysignaling is repressed and fibroblasts undergo myofibroblast conversion. Induction of specialized matricellular proteins that modulate growth factor and cytokine responses plays a critical role in activation of reparative cells and in formation of the scar. Cross-linking of the collagen-based matrix marks the end of the proliferative phase, as the scar matures and most fibroblasts and vascular cells in the wound undergo apoptosis. This chapter provides an overview of the phases of repair in the infarcted heart. Moreover, we discuss challenges and opportunities in targeting the inflammatory and reparative response following infarction in order to attenuate adverse remodeling and to prevent progression of post-infarction heart failure.
ASJC Scopus subject areas