Macrophage MR deficient model
Monocytes/macrophages play an important role in the clearance of apoptotic cells, the release of cytokines, proteases and the modulation of oxidative stress, contributing to wound repair process (Weinberger and Schulz, 2015). Myeloid MR is a key regulator of CV inflammation, fibrosis and hypertrophy (Rickard et al., 2009; Usher et al., 2010; Fraccarollo et al., 2011). Thus, macrophage-specific MR-null mice exhibited an altered expression of pro-inflammatory molecules (Rickard and Young, 2009; Usher et al., 2010; Bienvenu et al., 2012). MR deletion in macrophages protected against L-NAME/angiotensin II-induced cardiac hypertrophy, cardiac and vascular macrophage recruitment, inflammation and fibrosis (Usher et al., 2010). Myeloid cell-restricted MR deficiency led to improved healing and cardiac remodeling after ischemic injury trough the promotion of neutrophil efferocytosis, the suppression of superoxide production and the modulation of fibroblasts activation (Fraccarollo et al., 2019). MR knock-out prevented the upregulation of NGAL in infarct macrophages. Genetic ablation of myeloid MR reduced infarct size and inflammation after transient middle cerebral artery occlusion, whereas myeloid MR-knockout mice were not protected from permanent middle cerebral artery occlusion (Frieler et al., 2012). These studies using specific macrophage MR-null mice highlight that MR signaling in the myeloid cell population is essential for the pro-inflammatory and pro-fibrotic CV phenotype.