The major findings of the present study were that EC-Klf2 signal mediates the inhibitory effects of simvastatin on pathological myocardial fibrosis and hypertrophy and improvement of cardiac dysfunction via direct suppression of TGFβ1 or through EC-Klf2-Foxp1-TGFβ1 pathway, thus revealing a novel cholesterol lowering independent mechanism for simvastatin in the prevention of cardiac dysfunction progression to HF during the process of myocardial remodeling in the TAC pressure overloading model. This evidence concerns the gene TGFB1 and hydrops fetalis.