细胞焦亡是近年来被发现的一种新型程序性细胞死亡方式，其特征为依赖半胱天冬酶-1(caspase-1)并伴有大量促炎症因子释放。研究表明OX-LDL可通过调节细胞焦亡进而影响AS发生发展，lncRNA可能介导OX-LDL调节AS的发生发展，MLKL可通过调节细胞焦亡过程影响AS的进展。我们的前期预实验结果证明OX-LDL可上调lincRNA-FA2H-2和MLKL表达并促进细胞焦亡，过表达lincRNA-FA2H-2能明显促进MLKL表达和巨噬细胞焦亡。因此我们提出lincRNA-FA2H-2-MLKL途径可能介导OX-LDL调控细胞焦亡从而影响AS发生发展。本项目拟通过增强/抑制lincRNA-FA2H-2和/或MLKL表达，观察OX-LDL-lincRNA-FA2H-2-MLKL途径对细胞焦亡和AS的影响并探讨相关机制，为确定该途径可作为调控细胞焦亡和防治AS的新靶点提供科学依据。

Pyroptosis is a newly found form of programmed cell death, which is dependent on caspase-1 activation and leads to the release of pro-inflammatory cytokines. It is well established oxidized low-density lipoprotein (OX-LDL) promotes caspase-1 mediated pyroptotic cell death and plays a crucial role in the initiation and progression of atherosclerosis, and long non-coding RNA (lncRNA) might involve in OX-LDL-induced atherosclerosis development. In addition, atherosclerosis development can be affected by the mixed lineage kinase domain-like protein (MLKL) through regulating pyroptosis. Our preliminary data showed that expression levels of lincRNA-FA2H-2 and MLKL were significantly up-regulated and pyroptosis was increased in OX-LDL-induced THP-1 macrophages. Moreover, we demonstrated that MLKL expression levels and pyroptosis were markedly up-regulated by overexpression of lincRNA-FA2H-2 in THP-1 macrophages. Thus, we hypothesize that pyroptosis and atherosclerosis development can be affected by OX-LDL through inducing lincRNA-FA2H-2 and MLKL expression. In this study, we aim to explore the effect and mechanism of OX-LDL-lincRNA-FA2H-2-MLKL pathway on pyroptosis and atherosclerosis development by enhancing or inhibiting expression of lincRNA-FA2H-2 and/or MLKL. Therefore, our study may provide a new scientific evidence to establish OX-LDL-lincRNA-FA2H-2-MLKL pathway as a new target for regulation of pyroptosis and prevention of atherosclerosis.