Role of Epac in cardiac fibrosis and its clinical application for heart failure

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In order to examine the role of Epac1 (exchange protein directly activated by cyclic AMP) on cardiac fibrosis, chronic isoproterenol (ISO) infusion (60mg/kg/day for 7 days) was performed in Epac1-null mice (Epac1KO) and wild-type controls (WT). Cardiac fibrosis was significantly inhibited in Epac1KO, compared to WT. In order to examine the mechanism, we examined the role of Epac1 in the following 3 steps : Step-1) Production of collagen fiber Step-2) Cross-linking of collagen fiber by lysyl oxidase (LOX) Step-3) Degradation of collagen fiber by matrix mettaloproteinase (MMT). Our data in this study shows that cardiac fibrosis was reduced through the inhibition of step-3.