动脉粥样硬化是发生在动脉内膜的慢性炎症疾病，严重危害人类健康，但该疾病发病的分子机制仍不清楚。我们前期发现人源抗菌肽LL-37和线粒体DNA（mtDNA）形成的复合物是导致该疾病发生的重要原因（Immunity. 2015.43(6):1137-47；专利：ZL201410673406.6），但LL-37诱导动脉粥样硬化发病的机理仍不完全清楚。我们近期在LL-37诱导动脉粥样硬化发病方面又有新发现，一方面LL-37可以通过和低密度脂蛋白（LDL）的载脂蛋白B-100作用影响巨噬细胞对LDL的吞噬，另一方面LL-37也可以直接诱导血小板的聚集。本项目将在上述基础上研究：1）LL-37对细胞吞噬LDL的影响及机制；2）LL-37对血小板激活的影响及其对血小板与内皮细胞粘附的影响；3）LL-37-DNA复合物被识别的信号加工机制。本研究有助于阐明LL-37促进动脉粥样硬化发病的分子机制。

Atherosclerosis is a chronic inflammatory disease of the arterial wall, which is severely harmful to the health of mankind, the molecular mechanism of the disease is still unclear. We have demonstrated that the LL-37- mitochondrial DNA (mtDNA) complex acts as a key mediator of atherosclerosis formation (Immunity. 2015.43(6):1137-47; patent: ZL201410673406.6). Here we found that by binding with ApoB-100, the main apolipoprotein of LDL, LL-37 promotes macrophage engulfing more LDL. Moreover, LL-37 directly inhibited platelet aggregation, suggesting two novel roles of LL-37 in pathogenesis of atherosclerosis. The present project will focus on: 1. effect of LL-37 on engulfing LDL and the mechanism of it; 2. effects of LL-37 on platelet activation and adhesion of platelet to endothelial cell; 3. how does LL-37-DNA get access to the cell and the process of signal recognition of it. This project will facilitate understanding the mechanism of LL-37 driving atherosclerotic lesion formation.