Here we reported that TGF-β can induce Prrx1 S-nitrosylation in cardiac fibroblasts and further demonstrated that enforced expression of S-nitrosylation-resistant Prrx1, which is resistant to S-nitrosylation, has a marked protective effect against cardiac fibrosis and heart dysfunctions following MI. Here, TGFB1 is linked to myocardial infarction.