Vascular smooth muscle cell MR deficient models
Arterial stiffening is associated with altered arterial function with
decreased distensibility and modified wall structure contributing to HF
development (Lacolley et al., 2009). Moreover, VSMC MR regulated
hypertensive responses to vasoactive substances, vascular contractility
and oxidative stress (McCurley et al., 2012). Selective VSMC MR
deficient mice exhibited lower blood pressure. Aldosterone-salt
treatment did not modify arterial stiffness in mice with VSMC-specific
MR deletion, suggesting that vascular smooth muscle MR may be required
to adapt arterial stiffness to stress (Galmiche et al., 2014).
Accordingly, VSMCs-restricted MR deficiency protected from
aldosterone-induced vascular fibrosis (Pruthi et al., 2014). Moreover,
specific deletion of MR in VSMCs improved LV dysfunction and remodeling
after MI in a similar proportion than finerenone (Gueret et al., 2016).
Cell-specific MR ablation in VSMCs also improved cardiac blood supply in
a pressure-overload model and diminished the adverse cardiac remodeling
and cardiac dilation (Kim et al., 2021).
Specific MR loss in VSMCs led to lower blood pressure levels in aged
mice (McCurley et al., 2012) and decreased the expression of
pro-fibrotic genes in the aging vasculature (Kim et al., 2018).
Moreover, long-term treatment of aged mice with MR antagonist prevented
the progression of vascular stiffening, reduced vascular fibrosis and
induced a similar anti-fibrotic gene signature as VSMC-MR gene deletion
(Kim et al., 2018).