Abstract 11312: Regulatory T Lymphocyte Transfer Attenuates Cardiac Dysfunction after Myocardial Ischemia in Mice
Introduction: Downregulation of CD4+CD25+ regulatory T lymphocyte (Treg) has been found in local atherosclerotic lesions and in patients with myocardial infarction (MI). However, the roles of Treg in MI and the following inflammatory response have not yet been well elucidated.
Hypothesis: We assessed the hypothesis that adoptive transfer of Treg in mice with MI could attenuate cardiac inflammation following fibrosis after MI, and attenuate cardiac dysfunction.
Methods and Results: To clarify the role of Treg in MI, we conducted adoptive Treg transfer into model mice, in which the left anterior descending coronary artery (LAD) was ligated. Soon after the operation, mice were given a single intravenous injection of Treg and sacrificed on day 14 (Treatment, n=6). Other mice were operated on as described above for control, given saline and sacrificed on day 14 (Control, n=7). Heart rate, blood pressure, echocardiogram, histopathology, and molecular examination were performed. Heart rate and systolic blood pressure were not affected by Treg transfer. Echocardiogram showed improvement of anterior and posterior wall movement and also left ventricular fractional shortening (Control 27±1.8%, Treatment 40±1.6%, p<0.05). Histopathology with Mallory staining showed attenuated expansion of fibrosis (fibrosis per whole area, Control 43.4±5.7%, Treatment 18.1±2.0%, p<0.05), and this result was compatible to the echocardiogram. RT-PCR showed the mRNA levels of IFN-gamma in hearts on day 3 were significantly lower (Relative Quantitation; Control 0.19±0.025, Treatment 0.097±0.010, p<0.05) and Foxp3 in spleens on day 1 were significantly higher (Relative Quantitation; Control 3.31±1.28, Treatment 8.50±1.65, p<0.05) in the treatment group than in the control group.
Conclusions: We showed that adoptive Treg transfer could attenuate cardiac dysfunction after MI by preventing expansion of inflammation and fibrosis. These data suggest that Treg plays a beneficial role in ventricular remodeling after MI.
- © 2010 by American Heart Association, Inc.