Myocardial infarction is the most common cause of cardiac injury and results in 
acute loss of a large number of myocardial cells. Because the heart has 
negligible regenerative capacity, cardiomyocyte death triggers a reparative 
response that ultimately results in formation of a scar and is associated with 
dilative remodeling of the ventricle. Cardiac injury activates innate immune 
mechanisms initiating an inflammatory reaction. Toll-like receptor-mediated 
pathways, the complement cascade and reactive oxygen generation induce nuclear 
factor (NF)-kappaB activation and upregulate chemokine and cytokine synthesis in 
the infarcted heart. Chemokines stimulate the chemotactic recruitment of 
inflammatory leukocytes into the infarct, while cytokines promote adhesive 
interactions between leukocytes and endothelial cells, resulting in 
transmigration of inflammatory cells into the site of injury. Monocyte subsets 
play distinct roles in phagocytosis of dead cardiomyocytes and in granulation 
tissue formation through the release of growth factors. Clearance of dead cells 
and matrix debris may be essential for resolution of inflammation and transition 
into the reparative phase. Transforming growth factor (TGF)-beta plays a crucial 
role in cardiac repair by suppressing inflammation while promoting myofibroblast 
phenotypic modulation and extracellular matrix deposition. Myofibroblast 
proliferation and angiogenesis result in formation of highly vascularized 
granulation tissue. As the healing infarct matures, fibroblasts become apoptotic 
and a collagen-based matrix is formed, while many infarct neovessels acquire a 
muscular coat and uncoated vessels regress. Timely resolution of the 
inflammatory infiltrate and spatial containment of the inflammatory and 
reparative response into the infarcted area are essential for optimal infarct 
healing. Targeting inflammatory pathways following infarction may reduce 
cardiomyocyte injury and attenuate adverse remodeling. In addition, 
understanding the role of the immune system in cardiac repair is necessary in 
order to design optimal strategies for cardiac regeneration.