We show for the first time that: (i) treatment with NO2-OA significantly improves left ventricular systolic function; (ii) the extensive myocardial fibrosis in Mlp−/− mice is attenuated by NO2-OA; (iii) TGFβ signaling is increased in Mlp−/− mice and (iv) NO2-OA prevents TGFβ-mediated transdifferentiation and phosphorylation of downstream targets in isolated primary cardiac fibroblasts. This evidence concerns the gene TGFB1 and Myocardial fibrosis.