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Cardiomyocyte-derived CXCL12 is not involved in cardiogenesis but plays a crucial role in myocardial infarction

Item Type:Article
Title:Cardiomyocyte-derived CXCL12 is not involved in cardiogenesis but plays a crucial role in myocardial infarction
Creators Name:Mühlstedt, S. and Ghadge, S.K. and Duchene, J. and Qadri, F. and Järve, A. and Vilianovich, L. and Popova, E. and Pohlmann, A. and Niendorf, T. and Boyé, P. and Özcelik, C. and Bader, M.
Abstract:The chemokine CXCL12/SDF-1 is crucial for heart development and affects cardiac repair processes due to its ability to attract leukocytes and stem cells to injured myocardium. However, there is a great controversy whether CXCL12 is beneficial or detrimental after myocardial infarction (MI). The divergence in the reported CXCL12 actions may be due to the cellular source and time of release of the chemokine after MI. This study was designed to evaluate the role of cardiomyocyte-derived CXCL12 for cardiogenesis and heart repair after MI. We generated two rodent models each targeting CXCL12 in only one cardiac cell type: cardiomyocyte-specific CXCL12-overexpressing transgenic (Tg) rats and CXCL12 conditional knockout (cKO) mice. Animals of both models did not show any signs of cardiac abnormalities under baseline conditions. After induction of MI, cKO mice displayed preserved cardiac function and remodeling. Moreover, fibrosis was less pronounced in the hearts of cKO mice after MI. Accordingly, CXCL12 Tg rats revealed impaired cardiac function post-MI accompanied by enhanced fibrosis. Furthermore, we observed decreased numbers of infiltrating Th1 cells in the hearts of cKO mice. Collectively, our findings demonstrate that cardiomyocyte-derived CXCL12 is not involved in cardiac development but has adverse effects on the heart after injury via promotion of inflammation and fibrosis.
Keywords:CXCL12, Hypertrophy, Myocardial Infarction, Fibrosis, Inflammation, Animals, Mice, Rats
Source:Journal of Molecular Medicine
Page Range:1005-1014
Date:September 2016
Official Publication:https://doi.org/10.1007/s00109-016-1432-1
PubMed:View item in PubMed

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