心肌纤维化是多种心血管疾病共有的病理基础，也是心脏功能由代偿期向失代偿期转变的关键，其严重程度和疾病的发生发展及预后密切相关。交感-肾上腺素系统过度激活（激活β-ARs）是促心肌纤维化和心衰的形成的重要因素，β-ARs阻滞剂能够显著改善患者的预后。前期工作中我们在异丙肾上腺素（ISO）诱导的心肌重塑模型中利用蛋白质组学方法，发现了一个新的与心肌纤维化相关的蛋白质HIP-55。目前，HIP-55在心肌纤维化中的功能和机制尚无研究。我们前期实验提示HIP-55具有抑制ISO诱导心肌纤维化的功能，并能负调控IS0激活的adenylyl cyclase /cAMP/ p38 信号通路。因此，我们提出HIP-55通过负调控adenylyl cyclase/cAMP/ p38信号通路抑制心肌纤维化的科学假说。本课题将通过分子-细胞-整体动物不同层面研究，明确HIP-55在心肌纤维化中功能和调控机制。

Cardiac fibrosis is a common pathophysiological process shared by many cardiovascular diseases and is crucial in the transition of cardiac function from compensated to decompensated stage. It is closely related to the occurrence, development and prognosis of thesediseases. The excessive activation of Sympathoadrenal system(especially activation of β-ARs) is an important cause of cardiac fibrosis and heart failure,while β-ARs blockers can observably improve the prognosis for patients. HIP-55 is a novelprotein relatedto cardiac fibrosis, found by using proteomics approaches in the model of isoproterenol (ISO) induced cardiac remodeling in our former research. But the protein's effect in cardiac fibrosisand the mechanism are still unclear. Our previous researches indicate that HIP-55 can both inhibit ISO induced cardiac fibrosis and negatively regulate the signal of adenylyl cyclase /cAMP/ p38MAPK pathway. Therefore, this research hypothesized that HIP-55 can inhibit cardiac fibrosis by negatively regulating the signal of adenylyl cyclase /cAMP/ p38MAPK pathway, and will clarify the effect and the regulation mechanismof HIP-55 in cardiac fibrosis, on different levels of molecular, cellular and in vivostudies.