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).