Mineralocorticoid receptor blockade reduced aneurysm
formation induced by Ang II administration in CCN2-KO
As aldosterone biosynthetic process was one of the most BP enriched
terms in the deregulated genes from CCN2-KO mice (Table 2 ) we
investigated whether aldosterone pathway activation in CCN2 deficient
mice could contribute to aneurysm formation and rupture in presence of
Ang II. To this purpose, a new experiment included an additional group
of CCN2-KO mice treated with the mineralocorticoid receptor antagonist
spironolactone in combination with Ang II infusion. As previously
described with other mineralocorticoid receptor antagonist, eplerenone,
(Kurobe et al., 2013) spironolactone administration did not prevent
blood pressure increase induced by Ang II (Figure 7A ). However,
the reduction of aortic aneurysm formation and the improved survival
curve in presence of spironolactone suggested a role of aldosterone in
this process (Figure 7B and C ). In line with this finding,
spironolactone decreased both MMP-2 and MMP-9 activity in Ang II-infused
CCN2-KO mice (Figure 7D ).