Cardiomyocyte MR deficient model
There is strong evidence that specific MR blockade in cardiomyocytes exerts beneficial effects against pathological conditions. Mice lacking specifically cardiomyocyte MR presented cardiac hypertrophy accompanied by distinct changes in myocytes gene expression, with normal systolic and diastolic functions (Lother et al., 2011). Moreover, under pathological conditions, selective cardiomyocyte MR deficiency improved infarct healing and protected against progressive adverse remodeling and molecular alterations (Fraccarollo et al., 2011). Cardiomyocyte-specific inactivation of MR accelerated inflammation and endothelial cell response of wound repair, as well as enhanced infarct neovascularization. Cardiomyocyte MR deficient mice also presented a reduction in cardiac oxidative stress, fibrosis and apoptosis. All the above molecular and histological features contributed to a reduced infarct expansion, LV dilation and myocardial wall stress, leading to an improvement in cardiac remodeling, contractile dysfunction and HF (Fraccarollo et al., 2011).
MR cardiomyocyte-null mice treated with DOCA/salt were protected from cardiac fibrosis and inflammation (Rickard et al., 2012). Interestingly, cardiomyocyte MR ablation protected mice from cardiac dilation and failure but did not protect against cardiac hypertrophy, fibrosis, apoptosis or inflammation after chronic pressure overload (Lother et al., 2011). In line with these findings, cardiomyocyte MR deletion prevented doxorubicin-induced LV dysfunction but did not protect from myocardial fibrosis (Lother et al., 2018a).