Adjusting Macrophages to an Anti-Inflammatory Phenotype Improves Pathology Following a Heart Attack
Macrophages of the innate immune system can adopt a variety of behavior packages in response to circumstances. The most commonly studied are M1 (aggressive and inflammatory) versus M2 (anti-inflammatory and regenerative), as these capture two of the most interesting aspects of these immune cells. Macrophages hunt and destroy pathogens and rogue cells in their M1 form, but also participate in tissue maintenance and repair in their M2 form. A sizable number of research and development programs are based on ways to persuade M1 macrophages in injured tissues to switch into the M2 phenotype, resulting in improved regeneration and reduced harmful inflammation. Here, researchers show that their approach to this switching of phenotype can improve outcomes in a rat model of heart attack.
The modulation of inflammatory responses plays an important role in the pathobiology of cardiac failure. In a natural healing process, the ingestion of apoptotic cells and their apoptotic bodies by macrophages in a focal lesion result in resolution of inflammation and regeneration. However, therapeutic strategies to enhance this natural healing process using apoptotic cell-derived biomaterials have not yet been established.
In this study, apoptotic bodies-mimetic nanovesicles derived from apoptotic fibroblasts (ApoNVs) conjugated with dextran and ischemic cardiac homing peptide (CHP) (ApoNV-DCs) for ischemia-reperfusion (IR)-injured heart treatment are developed. Intravenously injected ApoNV-DCs actively targeted the ischemic myocardium via conjugation with CHP, and are selectively phagocytosed by macrophages in an infarcted myocardium via conjugation with dextran. ApoNV-DCs polarized macrophages from the M1 to M2 phenotype, resulting in the attenuation of inflammation.
Four weeks after injection, ApoNV-DCs attenuated cardiac remodeling, preserved blood vessels, and prevented cardiac function exacerbation in IR-injured hearts. Taken together, the findings may open a new avenue for immunomodulation using targeted delivery of anti-inflammatory nanovesicles that can be universally applied for various inflammatory diseases.