新近发现：自噬是调控动脉粥样硬化(AS)中细胞存活和斑块稳定的关键因素，而乙酰化修饰是调节自噬的重要方式之一。我们前期研究发现：组蛋白去乙酰化酶Sirt1通过去乙酰化作用抑制AS中血管外膜细胞的凋亡。因此，我们假设Sirt1的去乙酰化修饰对AS中血管外膜自噬有调控作用。本项目运用ApoE-/-/ Sirt1-/+ 小鼠、血管外膜相关细胞，通过对AS过程中血管外膜自噬现象的观察，明确AS中外膜异常引发的自噬是促进细胞存活还是诱导凋亡/死亡；通过Sirt1对AS中自噬的影响和机制研究，揭示Sirt1去乙酰化修饰对AS中自噬调节是直接作用或通过核转录因子FoxO1、NF-κB等进行调控；进一步比较Sirt1对血管外膜自噬和凋亡的调节作用是否存在相关性，阐明AS中Sirt1去乙酰化修饰对细胞自噬与凋亡的关系。该研究不仅为乙酰化修饰对AS中细胞自噬、凋亡的调节提供依据,而且为临床应用奠定实验基础。

Recent studies indicated that autophagy plays a key role in cell survival/death and plaque stability in the pathogenesis of atherosclerosis (AS). Acetylation is one of the important ways of regulating autophagy. Sirtuin 1 (Sirt1) belongs to a highly conserved family of nicotinamide adenine dinucleotide-dependent (NAD+-dependent) histone deacetylase. Our previous study found that Sirt1 inhibited vascular adventitia fibroblasts apoptosis in AS. Therefore, we hypothesize that Sirt1 regulate vascular adventitia autophagy by deacetylating its target proteins during atherogenesis. The effects of Sirt1 on vascular adventitia autophagy are determined in ApoE-/-/ Sirt1-/+ mice and vascular adventitial related cells. Further we study whether Sirt1 regulate cell autophagy directly or by deacetylating FoxO1、NF-κB、 mTOR and FoxO3. The relation between vascular adventitia autophagy and apoptosis will also be clarified. The study not only provides new theoretical bases for the regulation of acetylation on cell autophagy and apoptosis in AS, but also lays the foundation for clinical application.