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Regulation of Hepatic Cell Mobilization in Experimental Myocardial Ischemia

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Abstract

Myocardial ischemia induces cardiomyocyte injury and death, resulting in impairment of cardiac function. The adult cardiomyocytes possess a limited capacity of protection in myocardial ischemia, and nonmyocytic cells can be activated to support myocardial protection. We recently demonstrated that hepatic cells were able to upregulate genes encoding secreted proteins and were mobilized to the circulatory system, potentially contributing to myocardial protection against ischemic injury. In this investigation, we tested the potential mechanisms by which hepatic cells were mobilized in experimental myocardial ischemia. Following the induction of myocardial ischemia, hepatic cells, including hepatocytes and biliary epithelial cells, were mobilized to the circulatory system with a peak population 1.9 ± 0.4% at day 5. The cytokine IL-6 was upregulated in the ischemic myocardium as well as the serum. IL-6 promoted leukocyte retention in the liver as demonstrated by an increase in liver-retained leukocytes in myocardial ischemia in wild type mice, reduced leukocytes in IL-6−/− mice, and restoration of leukocyte retention in response to IL-6 administration to IL-6−/− mice. Liver-retained leukocytes exhibited upregulation of MMP-2, which in turn mediated hepatic cell mobilization by degrading extracellular matrix. These observations suggest that IL-6-stimulated leukocytes mediate the mobilization of hepatic cells via releasing MMP-2 in myocardial ischemia.

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Acknowledgments

We would like to thank Dr. Stephen I. Levin of Northwestern University and Dr. Yan Chun Li of The University of Chicago for insightful suggestions for constructing the genetically modified mouse models. This work was supported by the National Science Foundation and American Heart Association.

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No funds in any form have been or will be received from a commercial party for the subject of this manuscript.

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  1. Biomedical Engineering Department, Northwestern University, 2145 Sheridan Road, Evanston, IL, 60208-3107, USA

    Shu Q. Liu, Brandon J. Tefft, Brian Zhang, Charley Liu & Yu H. Wu

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Liu, S.Q., Tefft, B.J., Zhang, B. et al. Regulation of Hepatic Cell Mobilization in Experimental Myocardial Ischemia. Cel. Mol. Bioeng. 4, 693–707 (2011). https://doi.org/10.1007/s12195-011-0197-4

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