自噬相关基因FAM176A调控心脏重塑及其机制的研究

Cardiac remodeling, which a large number of studies have shown that autophagy has a close relationship with, is the initial factor of heart failure. FAM176A is a recently discovered autophagy and apoptosis related molecular, but whether it is involved in the regulation of cardiac remodeling is unclear. The research goal is to prove that autophagy-related gene FAM176A can inhibit cardiac remodeling, and elucidate the molecular regulation mechanism. The main research includes: ① we establish systemic and cardiac specific inducible FAM176A knockout mice to observe on the condition of base and stress (ISO stimulation) FAM176A regulate cardiac autophagy lead to improving cardiac remodeling and its possible mechanisms. ② in vitro isolation of cardiomyocytes from FAM176A knockout mice and use cardiomyocyte hypertrophy induced by isoproterenol (ISO) to observe the effect of FAM176A autophagy and myocardial hypertrophy, and then clarify its regulation of the molecular mechanisms of cardiac hypertrophy and signal transduction pathways. The research create a new direction to study the function of the autophagy-related genes FAM176A, help to clarify the molecular mechanism of cardiac remodeling, and provide new ideas for the prevention and treatment of heart failure.

心脏重塑是心力衰竭发生的始动因素，越来越多的研究表明自噬与心脏重塑存在密切关系。FAM176A是一个新发现的调控自噬与凋亡的重要分子，但是否参与调控心脏重塑目前尚不清楚。本课题研究目标是证明自噬相关基因FAM176A具有抑制心脏重塑的作用，同时阐明其分子调控机制。主要研究内容包括：① 建立全身和条件性心脏特异FAM176A基因敲除小鼠，分别观察基础和应激状态（ISO诱导）下FAM176A对小鼠心脏重塑及功能的影响，并探讨其调控心脏重塑的可能途径。② 体外培养FAM176A基因敲除小鼠心肌细胞，采用ISO诱导心肌细胞肥大模型，观察FAM176A对心肌细胞肥大及自噬的影响，进而阐明其调控心肌细胞肥大的分子机制及信号转导途径。本课题不仅开辟了自噬相关基因FAM176A功能研究的新方向，而且有助于阐明心脏重塑的分子调控机制，为防治心力衰竭提供新思路。

心脏重塑是心力衰竭发生的始动因素，越来越多的研究表明自噬与心脏重塑存在密切关系。FAM176A基因又称Eva1a，是一个新发现的广泛作用于细胞自噬各阶段的重要分子，但是否参与调控心脏重塑尚不清楚。本课题旨在证明自噬相关基因FAM176A具有抑制心脏重塑的作用，同时阐明其分子调控机制。主要研究内容包括：建立制备可诱导型心肌特异性FAM176A基因敲除小鼠，观察FAM176A基因缺失对于成年小鼠心脏重塑及心功能的影响，并探讨其调控心脏重塑的可能途径。结果发现，成年小鼠FAM176A基因缺失可以导致心肌自噬受损及凋亡增加，最终引发心脏重塑和心脏功能下降，其机制可能与调控mTOR/P70S6K信号通路有关。此次研究不仅开辟了自噬相关基因FAM176A功能研究的新方向，而且有助于阐明心脏重塑的分子调控机制，为防治心力衰竭提供新思路。