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

为了研究Epac1（由环AMP直接激活的交换蛋白）在心脏纤维化中的作用，在Epac1缺失小鼠（Epac1KO）和野生型对照组（WT）中进行了慢性异丙肾上腺素（ISO）输注（60mg/kg/天，持续7天）。与WT相比，Epac1KO明显抑制了心脏纤维化。为了研究其机制，我们研究了Epac1在以下3个步骤中的作用：step1)胶原纤维的产生step2)通过lysyl氧化酶（LOX）交联胶原纤维step3)通过基质金属蛋白酶（MMT）降解胶原纤维。我们在本研究中的数据表明，通过抑制step-3，心脏纤维化得以减少。

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.