动脉粥样硬化（AS）微钙化是位于内膜镶嵌于斑块内<60μm的钙沉积灶，极易引起斑块破裂造成急性心脑血管事件的发生。CD137-CD137L信号是参与AS进展的关键分子。我们前期研究显示：CD137-CD137L信号诱发ApoE-/-小鼠斑块内点灶状微钙化的形成与自噬密切相关；体外激动CD137-CD137L能介导自噬小体出胞并促进平滑肌细胞外基质钙沉积及成骨表型转变。因此我们提出如下假说：CD137-CD137L信号通过调控自噬转归介导AS内膜微钙化形成。本研究在前期基础上以CD137-CD137L信号调控自噬启动微钙化形成为主线，在ApoE-/-小鼠和平滑肌细胞模型上，分别激动和抑制CD137-CD137L信号，观察该信号对自噬转归及微钙化形成的影响，明确CD137-CD137L信号如何调控自噬转归，阐明该信号调控自噬转归介导内膜微钙化形成机制。该研究有望为AS内膜微钙化防治带来新契机。

Atherosclerotic microcalcification is calcium deposition (< 60μm in diameter) which is located in the intimal and embedded in the plaque. It is an important cause of acute cardio- and cerebro-vascular events as it easily cause plaque rupture. Our previous studies showed that the spot mircrocalcification formation is closely related to autophagy in the atherosclerotic plaque of ApoE-/- mice induced by CD137-CD137L signal. In vitro, activation of CD137-CD137L signal can mediate autophagosome exocytosis and promote the osteogenic phenotype transformation of smooth muscle cells and extracellular matrix calcium deposition. Therefore, we hypothesize that CD137-CD137L signal mediated the formation of atherosclerotic microcalcification by modulating authophagic outcome. In this study, we focus on how CD137-CD137L signal initiates the formation of microcalcification through modulating autophagy. ApoE-/- mice and VSMCs were used as models to verify the effect of CD137-CD137L signal on autophagy and microcalcification. We aim to investigate how CD137-CD137L signal modulates autophagy, and reveal the mechanism of CD137-CD137L in the formation of microcalcification through modulating autophagic outcome. The study is expected to bring new opportunities for prevention and treatment of atherosclerotic intimal microcalcifuation.