我们发现高表达n-3多不饱和脂肪酸的Fat-1小鼠，经手术致心衰后表现减少心室腔扩张、维持射血分数、维持线粒体和PKC调控心肌丝功能，并和circ-PDE5a调高和circ-Inpp5a调低表达密切相关。临床上高血脂是心衰的主要病因，在给药控制后仍有约三分一的病人伴发高脂血症，这提示心衰与血脂密切关联。目前主动脉弓缩窄术单一因素建模不能很好的拟合心衰的病征和诱因。因此，本项目采用高脂血症的ApoE-/-小鼠及ApoE敲除小鼠与Fat-1小鼠杂交的子代ApoEnull/Fat-1鼠，经主动脉弓缩窄术建立压力超负荷合并高脂血症的心衰模型，率先从整体心功能到亚细胞器功能，从组织学到蛋白再到基因水平对该模型进行评价，并以环状RNA为重点多层面探讨内源性n-3多不饱和脂肪酸降低血脂、减慢心衰进程的调控机理，可望建立更符合临床心衰患者病征和发病诱因的动物模型，并为心衰防治提供新的靶标途径。

We recently discovered enriched endogenous n-3 PUFAs reduced ventricular enlargement, maintained ejection fraction, protected mitochondria and PKC-associated myofilament activation after surgery-induced heart failure in Fat-1 mice, which are highly associated with upregulation of the circ-PDE5a and downregulation of circ-Inpp5A. Clinically high blood lipid is the main cause of heart failure. Around one third of patients have hyperlipidemia even after taking anti hyperlipemic agents, indicating that heart failure is highly associated with lipid metabolism. The single-factor heart failure model induced by a transverse aortic constriction cannot represent the complexity of the heart failure syndromes. Therefore, the project proposes to generate a heart failure model combined with hyperlipidemia using transverse aortic constriction in ApoE knockout mice and offspring of ApoE knockout breeding with Fat-1 mice. With this newly developed model, we will understand various effects of circular RNAs on n-3 PUFAs in reducing lipid contents and retarding heart failure progress. We anticipate this model reproduces the syndromes and causative factors of heart failure, providing prevention and therapeutic strategies for heart failure.