The Journal of Physiological Sciences · Oct 30, 2026

Mineralocorticoid blockade mitigates aortic aneurysms in mice underexpressing transforming growth factor-β1

By Kakoki M, Hagaman JR, Terajima M et al.

Loss-of-function mutations in the component genes of transforming growth factor (TGF)-β signaling have been demonstrated to cause proximal aortic aneurysms in humans (Loeys-Dietz Syndrome). Recently, we have demonstrated that homozygous mice for the loss-of-function mutation in the Tgfb1 gene (Tgfb1L/L mice) develop proximal aortic aneurysms which is associated with elevated plasma aldosterone levels. Here we found that chronic oral administration of a mineralocorticoid receptor antagonist eplerenone substantially prevented aortic aneurysms and elongated lifespans in Tgfb1L/L mice. Amiloride, which caused depressor effects comparative to eplerenone, resulted in less protection against aneurysms and early deaths than eplerenone in Tgfb1L/L mice. The reduced aortic levels of pyridinoline and (iso)desmosine which are collagen and elastin stable crosslinks, and of the expression of their associated enzymes in Tgfb1L/L mice were significantly restored by the eplerenone administration. These results suggest that mineralocorticoid receptor blockade is useful to prevent aortic aneurysms and early deaths in Loeys-Dietz Syndrome.

doi.org/10.1016/j.jphyss.2026.100116Open accessPubMed 42998627Interventions