晚期支架内血栓(LST)可导致心肌梗死甚至猝死。LST 确切机制尚未阐明，多认为与内皮祖细胞（EPC）老化所致的支架内皮化不全有关。本课题组首次证实白细胞端粒长度的缩短与支架内皮覆盖不全有关。研究显示端粒的长度与细胞衰老密切相关，且炎症是造成其损伤和缩短的最主要因素之一。新近研究发现端粒结构和功能的维持依赖于保护复合体POT1-TPP1。前期动物研究我们发现支架内皮化延迟与炎症反应密切相关。因此，我们推测支架后局部和系统性炎症影响了POT1-TPP1的表达和功能，导致端粒缩短和EPC老化加速。这可能是LST的一个新机制。为证实这一假说，我们应用基因转染、流式细胞仪等技术，炎症刺激下观察EPC老化以及POT1-TPP1的表达，从整体和细胞两个层次，观察该复合体对EPC的衰老，增殖分化功能，支架内皮化的影响及机制。本课题将从新的视角阐明 LST发生的分子机制，并为 LST的防治提供新靶点。

Late stent thrombus (LST) can cause acute myocardial infarction, or even sudden death. However, the exact mechanism of LST has not been clarified yet. Incomplete stent endothelialization resulting from endothelial progenitor cell (EPC) senescence is considered as one of the most important mechanism related to LST. Our group has reported for the first time that leukocyte telomere length is inversely associated with the percent stent strut coverage, but the mechanism is unclear. Previously studies have demonstrated that telomere length which is closely related to cell senescence determines the age of cells. Moreover, Inflammation is one of the most important injury factors thus lead to telomere shortening. While latest researches have found that POT1-TPP1 telomere protein complex which binding to the telomere DNA terminus can maintain normal structure and function of telomere as a result of protecting telomere from shortening and being damaged. Our previous animal study has showed that there is a close relationship with stent endothelialization delay and inflammation. Therefore, we deduce that local and systematic inflammation after stent implantation can alter the expression of POT1-TPP1 protein complex which ultimately accelerate telomere attrition and EPC senescence. This may be a new mechanism of LST. To validate our hypothesis, we investigate the effect of POT1-TPP1 on telomere length, as well as the proliferation and differentiation of EPC and pathway involved by alteration of POT1-TPP1 level using techniques such as gene transfer, flow cytometry and so on. This study will clarify a new molecular mechanism of LST and thus provide a new target for prevention and control.