In addition, several studies report losartan attenuates expression of TGF-β activators in a mouse model of Marfan syndrome [56], and improves connective tissue abnormalities in systemic sclerosis [57], which could involve in gene expression of metalloproteinases, fibrillin-1 and COL1A1 in SMAD4 mutations causing Myhre syndrome [58]. This evidence concerns the gene SMAD4 and systemic sclerosis.