Räuber Saskia, Fischer Maximilian, Messerer Denise, Wimmler Vanessa, Konda Kumaraswami, Todica Andrei, Lorenz Michael, Titova Anna, Schulz Christian, Weinberger Tobias
Medical Clinic I., Department of Cardiology, University Hospital, Ludwig Maximilian University, 81377 Munich, Germany.
Department of Neurology, Medical Faculty, Heinrich Heine University of Düsseldorf, 40225 Düsseldorf, Germany.
Biomedicines. 2022 May 30;10(6):1274. doi: 10.3390/biomedicines10061274.
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, RXRα 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 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 in monocytes and macrophages to determine its role in ischemia-reperfusion injury. We show that reduced expression of 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 levels in monocytes and macrophages negatively impacts cardiac remodeling after myocardial infarction. Thus, RXRα might represent a therapeutic target to regulate the immune response after MI in order to improve cardiac remodeling.
视黄酸X受体（RXRs）作为核受体类固醇/甲状腺激素超家族的成员，是健康和疾病期间免疫反应的关键调节因子。RXR亚型的表达取决于组织和细胞类型，RXRα是单核细胞和巨噬细胞中的相关亚型。先前的研究评估了RXRs的不同功能，并描述了RXR激动剂对缺血性损伤后结局的积极影响。然而，迄今为止，单核吞噬细胞中RXRα表达降低对心肌梗死后心脏重塑的影响尚未得到研究。在此，我们通过在单核细胞和巨噬细胞中进行时间控制的RXRα缺失来确定其在缺血再灌注损伤中的作用。我们发现，单核吞噬细胞中RXRα表达降低会导致吞噬活性降低和心肌中凋亡细胞积累，减少梗死边界区/梗死区域的血管生成和心脏巨噬细胞增殖，并影响单核细胞/巨噬细胞亚群组成。这些变化与缺血/再灌注损伤30天后更大的心肌缺损有关。总体而言，单核细胞和巨噬细胞中RXRα水平的降低对心肌梗死后的心脏重塑产生负面影响。因此，RXRα可能是调节心肌梗死后免疫反应以改善心脏重塑的治疗靶点。
