Abstract 12362: Regulatory T Cells Reduce Infarct Size, Improve LV Remodeling and Function after Myocardial Infarction in Mice
Introduction Ischemic cardiac damage is accompanied by upregulation of cardiac pro-inflammatory cytokines, as well as invasion of leukocytes and lymphocytes into the heart. Regulatory T cells (Tregs) are known to exert a suppressive effect on several immune cell types. We aimed to test the hypothesis that Tregs improve cardiac function after myocardial infarction (MI).
Methods and Results The number and function of suppressive activity of Tregs were assayed in mice subjected to experimental MI (n=40), and to hindlimb ischemia (n= 24). The numbers of splenocyte-derived Tregs were significantly higher after the injury, both in MI mice (16 ± 0.6% vs. 12 ± 0.7%, p < 0.01) and in hindlimb ischemia, (9.3±0.68% vs. 5±0.83%, p<0.001). Treg suppressive properties were not altered in MI mice, but were significantly reduced in mice underwent hindlimb ischemia. For adoptive transfer assays, Tregs (n=7) or PBS (n=7) were injected to the MI mice and their effect upon infarct size and cardiac function were compared. Compare with PBS, Treg transfer to MI mice reduced infarct size by masson's trichome staining (1.55 ± 0.4 mm2 vs. 4.1 ± 1.1 mm2, p = 0.03) and improved LV remodeling (LVSA, percent of change, 7.8 ± 16% vs. 101 ± 14%) and functional performance by echocardiography (fractional shortening, percent of change, 19.6 ± 18% vs. -32 ± 6%, p=0.02).
Conclusion Both cardiac and skeletal muscle ischemia increases the number of Treg cells. However, the suppression properties of Tregs were found to be reduced only after hindlimb ischemia. Our study demonstrates that after experimental MI, systemically Tregs are increased, migrate to the damaged area, and protect the infracted myocardium from subsequent negative LV remodeling and dysfunction.
- © 2012 by American Heart Association, Inc.