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.