Interleukin-13 Deficiency Aggravates Healing and Remodeling in Male Mice After Experimental Myocardial Infarction
Background—Activation of innate immunity, especially infiltration of monocytes, is critical for proper wound healing and scar formation after myocardial infarction (MI). Therefore, we tested the hypothesis that interleukin-13 (IL-13), which influences the differentiation of monocytes/ macrophages and has pro-fibrotic properties, modulates wound healing and remodelling after myocardial infarction.
Methods and Results—MI was induced by permanent ligation of the left coronary artery in both male and female WT/ IL-13-/- mice. Real-time-PCR demonstrated that expression of IL-13 was induced in left and right ventricular myocardium of WT mice within days in response to MI. 56-day survival was significantly impaired (65 % in WT vs 34% in IL-13-/-) in male but not female IL-13-/- (55 % in WT vs 54% in IL-13-/-) mice. Serial echocardiography showed significantly increased left ventricular dilation in male IL-13-/- compared to WT mice starting from day 1 after MI despite comparable infarct size. FACS analysis revealed less leukocyte infiltration in male IL-13-/- mice on day 3. Real-time-PCR analysis demonstrated reduced expression of marker genes of alternative activation in monocytes sorted from the infarct zone of male IL-13-/- in comparison to WT mice on day 3 after MI.
Conclusions—Genetic deficiency of IL-13 worsens outcome after MI in male mice. Our data indicate that IL-13 regulates leukocyte recruitment and induces M2-like monocyte/ macrophage differentiation which modifies wound healing within the infarct zone.
- Received July 3, 2013.
- Accepted June 13, 2014.