肌浆网钙泵（SERCA2a）是调节心肌收缩力的关键蛋白，其表达与功能受损是心脏泵功能障碍/心力衰竭发生的关键原因。LncRNAs是一类调节心脏疾病的关键分子，我们课题组新近发现LncRNA-ZFAS1通过抑制SERCA2a表达调节心脏功能（Circ Res，2018，共同作者）。申请人小组同期发现另一个调节心脏收缩功能的lncRNA（CFAL），前期结果如下： 1）CFAL在心力衰竭小鼠心脏中表达上调；2）CFAL转基因过表达小鼠的心脏功能明显减退，心肌细胞收缩力降低，SERCA2a蛋白表达减少；3）CFAL与转录因子SP-1和SERCA2a均相结合。我们假设：CFAL通过与SP-1和SERCA2a结合，减少SERCA2a蛋白的表达量，导致心肌细胞钙循环障碍、心力衰竭。我们将应用转基因、基因敲除模式动物以及多种分子生物学方法，从离体和在体水平阐明CFAL的功能，并揭示其分子调控机制。

Sarcoplasmic reticulum calcium pump (SERCA2a) is a key protein regulating myocardial contractility, and its impairment of expression and function is the critical reason for cardiac pump dysfunction / heart failure. LncRNAs is an important molecule regulating cardiac diseases. Recently, LncRNA-ZFAS1 has been shown to regulate cardiac function by inhibiting SERCA2a expression by our group(Circ Res, 2018, Co-author). My group found another cardiac systolic function related lncRNA (CFAL) at the same time. The preliminary results are as follows: 1) the expression of CFAL is upregulated in failure heart of mice; 2) Cardiac function of CFAL transgenic overexpression mice decreased significantly, with reduced myocardial contractility and expression of SERCA2a ; 3) CFAL binds to the transcription factor SP-1 and SERCA2a . We hypothesize that CFAL reduces the expression of SERCA2a by combining with SP-1 and SERCA2a, resulting in calcium handling disorder and heart failure . We will use transgenic, knockout animal models and various molecular biological methods to elucidate the function of CFAL both in vitro and in vivo, and reveal its molecular mechanism.