Immune Cell Modulation of Cardiac Remodeling

Abstract

Heart failure remains a critical target to improve the health of the US population. It is a major cause of morbidity and mortality in the United States.1 Heart failure is a result of acute or chronic injury followed by healing and remodeling that are insufficient to maintain or restore function. Myocardial infarction (MI) is the major cause of heart dysfunction, but other more chronic injuries, such as those caused by hypertension or genetic defects have many similarities. Article see p 1652 The response to injury in MI can be parsed into multiple overlapping phases (Figure 1). The initial phase involves an acute inflammatory response and includes recruitment of inflammatory cells and the clearance of dead tissue. A subsequent phase involves the initial reparative response replacing the lost tissue and includes immune cells that will both terminate the initial inflammatory response and begin repair.2 This repair is followed by a more prolonged phase of continued remodeling that involves both destruction and replacement of tissue. Remodeling is sensitive to the presence of continued stress, which can have adverse consequences. The innate immune system has recently been shown to be important in cardiac response to MI.2,3 However, a role for adaptive immunity responding to damage has also been suspected with protection from MI in animals treated with adoptive transfer of regulatory T cells.4 Figure 1. Phases of inflammation and healing after myocardial infarction and their alteration in transgenic models. The response to injury can be parsed into 3 phases: injury and inflammation, initial repair, and remodeling. Inflammation has associated proinflammatory leukocytes characterized by Ly-6Chi monocytes or classically activated macrophages (CAM; which would be CD206−). Healing myeloid cells include Ly-6Clo and alternatively activated macrophages (AAM; CD206+). Both monocytes and macrophages are active in the first week. …