血管平滑肌源性泡沫细胞形成是动脉粥样硬化病变的重要事件。已有研究表明自噬活性降低可促进泡沫细胞的形成，但机制尚需深入研究。我们预实验发现，平滑肌细胞泡沫化过程中自噬起始激酶ULK1的O-GlcNAc糖基化修饰水平明显升高，而抑制其O-GlcNAc糖基化修饰能显著抑制泡沫细胞形成。为此我们提出“O-GlcNAc糖基化修饰自噬起始激酶ULK1可以降低ULK1激酶活性，抑制细胞自噬，促使细胞内游离胆固醇持续堆积而无法外排，最终诱导血管平滑肌细胞泡沫化发生”。为证实上述假说，本项目以大鼠平滑肌源性泡沫细胞模型为对象，研究泡沫细胞形成过程中O-GlcNAc糖基化修饰ULK1与自噬的变化规律及相关性；鉴定ULK1激酶O-GlcNAc糖基化修饰位点，研究O-GlcNAc糖基化修饰对ULK1分子功能以及对泡沫细胞形成的调控机制。该研究将有助于阐明血管平滑肌泡沫化发生机制，为动脉粥样硬化防治提供理论基础。

The formation of vascular smooth muscle (VSMC)-derived foam cells is considered to be an important event in the late stages of atherosclerotic lesions. Several studies have shown that autophagy has a potential role in regulating foam cell formation, but the mechanism is not yet fully understood. Our preliminary experiments demonstrated that the O-GlcNAcylation levels of autophagy-initiation kinase ULK1 increased threefold during VSMC foam cell formation, while inhibiting O-GlcNAcylation of ULK1 significantly inhibited VSMC foam cell formation. Therefore, we assume that O-GlcNAcylation of the ULK1 may decrease kinase activity of ULK1, damage autophagy, promote intracellular accumulation of free cholesterol, and ultimately induce VSMC foam cell formation. To confirm this hypothesis, we will use VSMC foam cell model to investigate the O-GlcNAcylation levels of autophagy-initiation kinase ULK1, the autophagy activity and the relevance among them. Further, we will identify O-GlcNAcylated sites of ULK1 kinase and make an intensive study of regulation mechanism of O-GlcNAcylated ULK1 to autophagy and VSMC foam cell formation. Finally, we hope that this study will help to clarify the mechanism of VSMC foam cell formation and provide new insights of preventing atherosclerotic lesions.