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 ).