Of Mice and Dogs: Species-Specific Differences in the Inflammatory Response Following Myocardial Infarction

Oliver Dewald, Guofeng Ren, Georg D. Duerr, Martin Zoerlein, Christina Klemm, Christine Gersch, Sophia Tincey, Lloyd H. Michael, Mark L. Entman, Nikolaos G. Frangogiannis

Research output: Contribution to journalArticle

266 Scopus citations

Abstract

Large animal models have provided much of the descriptive data regarding the cellular and molecular events in myocardial infarction and repair. The availability of genetically altered mice may provide a valuable tool for specific cellular and molecular dissection of these processes. In this report we compare closed chest models of canine and mouse infarction/reperfusion qualitatively and quantitatively for temporal, cellular, and spatial differences. Much like the canine model, reperfused mouse hearts are associated with marked induction of endothelial adhesion molecules, cytokines, and chemokines. Reperfused mouse infarcts show accelerated replacement of cardiomyocytes by granulation tissue leading to a thin mature scar at 14 days, when the canine infarction is still cellular and evolving. Infarcted mouse hearts demonstrate a robust but transient postreperfusion inflammatory reaction, associated with a rapid up-regulation of interleukin-10 and transforming growth factor-β. Unlike canine infarcts, infarcted mouse hearts show only transient macrophage infiltration and no significant mast cell accumulation. In correlation, the growth factor for macrophages, M-CSF, shows modest and transient up-regulation in the early days of reperfusion; and the obligate growth factor for mast cells, stem cell factor, SCF, is not induced. In summary, the postinfarction inflammatory response and resultant repair in the mouse heart shares many common characteristics with large mammalian species, but has distinct temporal and qualitative features. These important species-specific differences should be considered when interpreting findings derived from studies using genetically altered mice.

Original languageEnglish (US)
Pages (from-to)665-677
Number of pages13
JournalAmerican Journal of Pathology
Volume164
Issue number2
DOIs
StatePublished - Feb 2004

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Dewald, O., Ren, G., Duerr, G. D., Zoerlein, M., Klemm, C., Gersch, C., Tincey, S., Michael, L. H., Entman, M. L., & Frangogiannis, N. G. (2004). Of Mice and Dogs: Species-Specific Differences in the Inflammatory Response Following Myocardial Infarction. American Journal of Pathology, 164(2), 665-677. https://doi.org/10.1016/s0002-9440(10)63154-9