Modulation of Rxr alpha Expression in Mononuclear Phagocytes Impacts on Cardiac Remodeling after Ischemia-Reperfusion Injury

Rauber, Saskia; Fischer, Maximilian; Messerer, Denise; Wimmler, Vanessa; Konda, Kumaraswami; Todica, Andrei; Lorenz, Michael; Titova, Anna; Schulz, Christian und Weinberger, Tobias (2022): Modulation of Rxr alpha Expression in Mononuclear Phagocytes Impacts on Cardiac Remodeling after Ischemia-Reperfusion Injury. In: Biomedicines, Bd. 10, Nr. 6

Abstract

Retinoid X receptors (RXRs), as members of the steroid/thyroid hormone superfamily of nuclear receptors, are crucial regulators of immune response during health and disease. RXR subtype expression is dependent on tissue and cell type, RXR alpha being the relevant isoform in monocytes and macrophages. Previous studies have assessed different functions of RXRs and positive implications of RXR agonists on outcomes after ischemic injuries have been described. However, the impact of a reduced Rxr alpha expression in mononuclear phagocytes on cardiac remodeling after myocardial infarction (MI) has not been investigated to date. Here, we use a temporally controlled deletion of Rxr alpha in monocytes and macrophages to determine its role in ischemia-reperfusion injury. We show that reduced expression of Rxr alpha in mononuclear phagocytes leads to a decreased phagocytic activity and an accumulation of apoptotic cells in the myocardium, reduces angiogenesis and cardiac macrophage proliferation in the infarct border zone/infarct area, and has an impact on monocyte/macrophage subset composition. These changes are associated with a greater myocardial defect 30 days after ischemia/reperfusion injury. Overall, the reduction of Rxr alpha levels in monocytes and macrophages negatively impacts cardiac remodeling after myocardial infarction. Thus, RXR alpha might represent a therapeutic target to regulate the immune response after MI in order to improve cardiac remodeling.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 491502892