To examine the role of Epac, a new beta-adrenergic signaling molecule, for the development of heart failure

众所周知，交感神经和儿茶酚胺信号随后被激活以补偿心功能障碍。儿茶酚胺的这种补偿机制传统上被理解为pka介导的心脏收缩力的增强。我们假设Epac作为cAMP信号的一个新的靶点，独立于PKA发挥作用，也起着关键作用。Epac1通过IL-6抑制心脏Jak-STAT通路和iNOS蛋白。cAMP/Epac通路的激活保护心脏免受细胞因子诱导的心功能障碍，提示儿茶酚胺信号在内毒素血症中补偿心功能障碍的新作用。

It is well known that sympathetic and thus catecholamine signal is activated thereafter to compensate cardiac dysfunction. The mechanism of such compensation by catecholamine has been traditionally understood as PKA-mediated enforcement of cardiac contractility. We hypothesized that Epac, a new target of cAMP signal that functions independently from PKA, also plays a key role. Epac1 inhibited the Jak-STAT pathway and iNOS protein in the heart in response via IL-6. Activation of the cAMP/Epac pathway protected the heart against cytokine-induced cardiac dysfunction, suggesting a new role of catecholamine signal in compensating cardiac dysfunction in endotoxemia.