血管内皮功能障碍与损伤在动脉粥样硬化（AS）的发生发展中具有重要作用。我们前期研究发现UFM1在AS模型小鼠主动脉壁中高表达，且UFM1具有抑制内皮细胞NF-κB入核、促进eNOS磷酸化、增强自噬和抑制细胞死亡的作用。同时，我们首次发现UFM1可以对PARP1进行翻译后修饰，但PARP1发生UFM1化修饰后下游生物学功能尚待明确。由此我们提出假设：血管内皮中PARP1的UFM1化修饰使PARP1活性下降，而后通过抑制炎症反应和增加NO合成改善血管内皮功能，通过促进自噬和减弱PARP1依赖性程序性细胞死亡改善血管内皮损伤，最终缓解AS病程。本研究拟在细胞和动物水平，通过分子生物学、细胞生物学和病理学等技术手段，揭示UFM1化修饰调控新的底物蛋白PARP1的酶活性，阐明PARP1的UFM1化修饰对AS病程中血管内皮功能障碍与损伤的影响，为寻找防治AS的靶点提供新的思路。

Vascular endothelial dysfunction and injury are essential contributors to the pathogenesis of atherosclerosis (AS). In our previous study, we have found that ubiquitin-fold modifier 1 (UFM1) was highly expressed in the aortic of atherosclerosis mice, and further found that UFM1 suppressed the nuclear translocation of nuclear factor-κB (NF-κB), promoted phosphorylation level of endothelial NO synthase (eNOS), enhanced autophagy and inhibited cell death in endothelial cells. Moreover, it was the first time that we observed the posttranslational modification of poly (ADP-ribose) polymerase (PARP1) by UFM1. Based on these findings, we hypothesize that, by modifying PARP1 and inhibiting its enzyme activity, UFM1 can affects endothelial function though regulating inflammatory response and NO synthesis and affects endothelial injury though regulating autophagy and PARP1 dependent programmed cell death, which ultimately retard the occurrence and development of AS. Collectively, in this study, we aim to reveal PARP1 is a new substrate protein of UFMylation, and to clarify the mechanism of PARP1 UFMylation on vascular endothelial dysfunction and injury at the cellular and animal level by means of molecular biology, cell biology and pathology, so as to provide a novel clue to the prevention and treatment of AS.