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Renin Inhibition Improves the Survival of Mesenchymal Stromal Cells in a Mouse Model of Myocardial Infarction

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Abstract

The aim of this study was to determine if renin inhibition is able to improve the survival of transplanted stem cells in a mouse model of myocardial infarction. Myocardial infarction was induced in FVB/NJ inbred mice (n = 23). Bone marrow-derived mouse mesenchymal stromal cells (mMSCs, 3 × 105) expressing the reporter gene firefly luciferase were delivered intramyocardially (n = 12) and monitored non-invasively by bioluminescence imaging. A group of these mice (n = 6) received aliskiren (15 mg/kg/day) via an osmotic pump implanted subcutaneously. The survival of mMSCs was significantly increased in those animals that received aliskiren leading to a significant improvement in systolic function after myocardial infarction. Histological analysis revealed a significant reduction in inflammation and collagen deposition in those mice that received aliskiren compared to controls. Renin inhibition of the ischemic myocardium is able to modulate the microenvironment improving the survival and efficacy of transplanted mMSCs in a mouse model of myocardial infarction.

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Acknowledgments

The authors would like to acknowledge Mr. Bruce Knudsen for his assistance with the non-invasive measurement of blood pressure and Mrs. Elise Oheler for her assistance with the high-resolution ultrasonography.

Conflict of Interest

None declared.

No human studies were carried out by the authors for this article.

All institutional and national guidelines for the care and use of laboratory animals were followed and approved by the appropriate institutional committees

Sources of Funding

Novartis and the Mayo Foundation.

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Authors and Affiliations

  1. Divisions of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USA

    Federico Franchi, Adachukwu Ezenekwe, Lukas Wellkamp, Karen M. Peterson, Amir Lerman & Martin Rodriguez-Porcel

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  1. Federico Franchi
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  2. Adachukwu Ezenekwe
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  3. Lukas Wellkamp
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  4. Karen M. Peterson
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  5. Amir Lerman
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  6. Martin Rodriguez-Porcel
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Correspondence to Martin Rodriguez-Porcel.

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Associate Editor Enrique Lara-Pezzi oversaw the review of this article

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Franchi, F., Ezenekwe, A., Wellkamp, L. et al. Renin Inhibition Improves the Survival of Mesenchymal Stromal Cells in a Mouse Model of Myocardial Infarction. J. of Cardiovasc. Trans. Res. 7, 560–569 (2014). https://doi.org/10.1007/s12265-014-9575-3

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  • DOI: https://doi.org/10.1007/s12265-014-9575-3

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