Ulrich Hofmann1, Susanne Knorr2, Benjamin Vogel2, Johannes Weirather2, Anna Frey2, Georg Ertl2, Stefan Frantz2. 1. From the Department of Internal Medicine I, University Hospital Würzburg, Germany, and Comprehensive Heart Failure Center, University of Würzburg, Germany. hofmann_u2@klinik.uni-wuerzburg.de. 2. From the Department of Internal Medicine I, University Hospital Würzburg, Germany, and Comprehensive Heart Failure Center, University of Würzburg, Germany.
Abstract
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 profibrotic properties, modulates wound healing and remodeling after MI. METHODS AND RESULTS: MI was induced by permanent ligation of the left coronary artery in both male and female wild-type (WT)/IL-13(-/-) mice. Real-time polymerase chain reaction demonstrated that expression of IL-13 was induced in left and right ventricular myocardium of WT mice within days in response to MI. Fifty-six-day survival was significantly impaired (65% in WT versus 34% in IL-13(-/-)) in male but not female IL-13(-/-) (55% in WT versus 54% in IL-13(-/-)) mice. Serial echocardiography showed significantly increased left ventricular dilation in male IL-13(-/-) compared with WT mice starting from day 1 after MI, despite comparable infarct size. Fluorescence-activated cell sorter analysis revealed less leukocyte infiltration in male IL-13(-/-) mice on day 3. Real-time polymerase chain reaction analysis demonstrated reduced expression of marker genes of alternative activation in monocytes sorted from the infarct zone of male IL-13(-/-) in comparison with 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.
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 profibrotic properties, modulates wound healing and remodeling after MI. METHODS AND RESULTS: MI was induced by permanent ligation of the left coronary artery in both male and female wild-type (WT)/IL-13(-/-) mice. Real-time polymerase chain reaction demonstrated that expression of IL-13 was induced in left and right ventricular myocardium of WT mice within days in response to MI. Fifty-six-day survival was significantly impaired (65% in WT versus 34% in IL-13(-/-)) in male but not female IL-13(-/-) (55% in WT versus 54% in IL-13(-/-)) mice. Serial echocardiography showed significantly increased left ventricular dilation in male IL-13(-/-) compared with WT mice starting from day 1 after MI, despite comparable infarct size. Fluorescence-activated cell sorter analysis revealed less leukocyte infiltration in male IL-13(-/-) mice on day 3. Real-time polymerase chain reaction analysis demonstrated reduced expression of marker genes of alternative activation in monocytes sorted from the infarct zone of male IL-13(-/-) in comparison with 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.
Authors: Alan J Mouton; Osvaldo J Rivera Gonzalez; Amanda R Kaminski; Edwin T Moore; Merry L Lindsey Journal: Pharmacol Res Date: 2018-10-28 Impact factor: 7.658
Authors: Jianrui Song; Ryan A Frieler; Steven E Whitesall; Yutein Chung; Thomas M Vigil; Lindsey A Muir; Jun Ma; Frank Brombacher; Sascha N Goonewardena; Carey N Lumeng; Daniel R Goldstein; Richard M Mortensen Journal: Am J Physiol Heart Circ Physiol Date: 2020-11-08 Impact factor: 4.733