Leukocyte-Mediated Cardiac Repair after Myocardial Infarction in Non-Regenerative vs. Regenerative Systems

Innate and adaptive leukocytes rapidly mobilize to ischemic tissues after myocardial infarction in response to damage signals released from necrotic cells. Leukocytes play important roles in cardiac repair and regeneration such as inflammation initiation and resolution; the removal of dead cells and debris; the deposition of the extracellular matrix and granulation tissue; supporting angiogenesis and cardiomyocyte proliferation; and fibrotic scar generation and resolution. By organizing and comparing the present knowledge of leukocyte recruitment and function after cardiac injury in non-regenerative to regenerative systems, we propose that the leukocyte response to cardiac injury differs in non-regenerative adult mammals such as humans and mice in comparison to cardiac regenerative models such as neonatal mice and adult zebrafish. Specifically, extensive neutrophil, macrophage, and T-cell persistence contributes to a lengthy inflammatory period in non-regenerative systems for adverse cardiac remodeling and heart failure development, whereas their quick removal supports inflammation resolution in regenerative systems for new contractile tissue formation and coronary revascularization. Surprisingly, other leukocytes have not been examined in regenerative model systems. With this review, we aim to encourage the development of improved immune cell markers and tools in cardiac regenerative models for the identification of new immune targets in non-regenerative systems to develop new therapies.