颈动脉斑块的破裂是导致脑卒中的重要原因。新近研究发现内皮间质转化（EndMT）与斑块稳定性转变密切相关，但EndMT发生的机制迄今未明。我们的前期研究发现，相比于稳定斑块，易损斑块中EndMT的程度显著上升，自噬程度显著降低，并通过RNA-seq发现易损斑块中β-arrestin2表达水平升高最为显著。在动物和细胞实验中发现，抑制内皮细胞β-arrestin2表达能够显著减轻高脂引起的自噬功能障碍以及EndMT。据此，我们提出假说：β-arrestin2表达升高抑制自噬激活,导致EndMT和颈动脉斑块稳定性转变。为验证以上假说，我们拟从临床、动物、细胞、分子四个层次，采用内皮细胞谱系示踪、RNA-seq、质谱等多种方法进行系统地论证并深入研究其分子机制。本课题的研究结果将为颈动脉斑块的稳定性转变研究提供全新的视角，为今后抑制易损斑块生成和预防斑块破裂的研究提供全新的理论基础及治疗方向。

The rupture of carotid plaque is one of the most important causes of stroke. Recent studies have demonstrated that endothelial-to-mesenchymal transition (EndMT) plays an important role in the shift of plaque stability. However, the underlying mechanism remains unclear. Our previous study found that, compared with stable plaques, EndMT increased significantly while autophagy decreased significantly in vulnerable plaques. And our RNA-seq results revealed that β-arrestin2 expression level increased most significantly in vulnerable plaques. Furthermore, our in vivo and in vitro results demonstrated that loss of β-arrestin2 significantly reduced autophagy dysfunction and EndMT caused by hyperlipidemia. Accordingly, we hypothesize that the increased expression of β-arrestin2 leads to the dysfunction of autophagy, and subsequently aggravates the degree of EndMT, which results in the shift of carotid plaque stability. To verify and further study the hypothesis above, a variety of in vivo and in vitro experiments, including endothelial lineage-tracking system, RNA-seq, mass spectrometry are employed. This study will provide a new perspective on mechanisms of plaque stability shift and a novel therapeutic way to prevent vulnerable plaque formation and rupture.