Abstract
Heart failure is a consequence of various cardiovascular diseases and associated with poor prognosis. Despite progress in the treatment of heart failure in the past decades, prevalence and hospitalisation rates are still increasing. Heart failure is typically associated with cardiac remodelling. Here, inflammation and fibrosis are thought to play crucial roles. During cardiac inflammation, immune cells invade the cardiac tissue and modulate tissue-damaging responses. Cardiac fibrosis, however, is characterised by an increased amount and a disrupted composition of extracellular matrix proteins. As evidence exists that cardiac inflammation and fibrosis are potentially reversible in experimental and clinical set ups, they are interesting targets for innovative heart failure treatments. In this context, animal models are important as they mimic clinical conditions of heart failure patients. The advantages of mice in this respect are short generation times and genetic modifications. As numerous murine models of heart failure exist, the selection of a proper disease model for a distinct research question is demanding. To facilitate this selection, this review aims to provide an overview about the current understanding of the pathogenesis of cardiac inflammation and fibrosis in six frequently used murine models of heart failure. Hence, it compares the models of myocardial infarction with or without reperfusion, transverse aortic constriction, chronic subjection to angiotensin II or deoxycorticosterone acetate, and coxsackievirus B3-induced viral myocarditis in this context. It furthermore provides information about the clinical relevance and the limitations of each model, and, if applicable, about the recent advancements in their methodological proceedings.
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The authors thank Katharina Scherschel for excellent help and support in microscopic imaging techniques.
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This work was funded by the German Ministry of Research and Education (DZHK, German Center of Cardiovascular Research), Grant number 81365-150.
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Bacmeister, L., Schwarzl, M., Warnke, S. et al. Inflammation and fibrosis in murine models of heart failure. Basic Res Cardiol 114, 19 (2019). https://doi.org/10.1007/s00395-019-0722-5
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DOI: https://doi.org/10.1007/s00395-019-0722-5