ADTRP调控FGF13/Caveolae影响心肌重构和血管重构的共同机理研究

心力衰竭是冠心病等心血管疾病的终末阶段，严重影响国人健康，揭示心力衰竭过程中心肌重构和血管重构等关键步骤的调控机制是有效预防和干预的前提。前期研究中，通过人群研究和已成功构建的组织特异性敲除小鼠模型，本课题组发现ADTRP基因能够同时调控血管重构和心肌重构等心力衰竭过程中关键表型，但具体机制未知，有待研究。ADTRP存在于小窝结构中，本课题组发现其影响小窝结构关键调控因子FGF13表达。基于以上研究基础，本课题拟基于动物模型和细胞模型，从整体-组织-细胞-分子层面，研究ADTRP是否通过FGF13调控小窝结构，进而同时调控心肌梗死后心脏血管重构和心肌重构的发生，并进一步探讨ADTRP作为心力衰竭干预靶点的可能性。通过本研究，有望明确ADTRP与心力衰竭表型之间的关联，揭示ADTRP基因调控心脏重构和心力衰竭表型的详细机理及其分子机制，并为寻找新的防治手段和治疗靶点打下基础。

Heart failure is the final outcome of cardiovascular diseases such as coronary heart disease, which seriously affects the health of Chinese people. It is the premise of effective prevention and intervention to reveal the mechanism of key steps such as myocardial remodeling and vascular remodeling in the process of heart failure. In previous studies, through population genetics and successfully constructed conditional knockout mouse, we found that ADTRP gene can simultaneously regulate key phenotypes in the process of heart failure such as vascular remodeling and myocardial remodeling, but the details is unknown and needs to be revealed. ADTRP exists in the caveolae, and our group found that ADTRP can affects the expression of FGF13, a key regulator of caveolae. Based on the above research basis, the current proposal intends to study whether ADTRP regulates the caveolae through FGF13 and then regulates the occurrence of cardiac vascular remodeling and myocardial remodeling after myocardial infarction based on animal model and cell model, and further discusses the possibility of ADTRP as an intervention target for heart failure. Through this study, it is expected to clarify the association between ADTRP and heart failure phenotype, reveal the detailed mechanism of ADTRP gene regulating cardiac remodeling and heart failure phenotype, and lay the foundation for finding new prevention and treatment methods and therapeutic targets.