Abstract 12020: Post Infarction Survival and Cardiac Remodeling in a Murine Model of Myocardial Infarction Depends on the Interplay of Interferon Gamma, Neutrophils and Inflammatory Monocytes
Background: Inflammatory myelomonocytic cells are involved in both the initial injury phase and the healing process of myocardial infarction (MI).
Objective: To investigate the effects of myelomonocytic cells for cardiac injury and healing in a murine model of MI by scheduled depletion of lysozyme M positive (LysM+) immune cells.
Methods and Results: MI was induced in 8 to 12 week old male C57BL/6 mice by ligation of the left anterior descending (LAD) coronary artery. Compared to sham operated LysMCre controls, LysMiDTR transgenic mice that had been depleted of LysM+cells for 3d prior MI by diphtheria toxin injection, revealed a decreased influx of CD45.2+/CD3-/CD11b+/Gr-1high neutrophils into infarcted myocardium 1d post MI. Despite discontinuation of the depletion regimen after LAD ligation, we observed a prolonged reduction of cardiac interferon gamma (INFγ) and tumor necrosis factor alpha mRNA expression as well as worsening of left ventricular ejection fraction (LVEF) until d28 post MI. Continuation of the depletion regimen aggravated the influx of inflammatory cells and led to premature death within 7d post MI. To more specifically assess the role of neutrophils, we depleted mice with a monoclonal anti-GR1 antibody. We found increased mortality early after MI as well as a decreased LVEF. LAD ligated INFγ-/- mice revealed a drastically decreased survival and a reduced LVEF, implicating a protective interplay of INFγ with GR1+ neutrophils in inflammatory response after MI.
Conclusion: Strategies to combat inflammation in MI must consider a potentially beneficial effect of early neutrophil influx into infarcted myocardium.
Author Disclosures: M.C. Knorr: None. S. Finger: None. S.H. Karbach: None. S. Kossmann: None. T. Schönfelder: None. T. Münzel: None. P. Wenzel: None.
- © 2014 by American Heart Association, Inc.