心血管并发症是引起早期乳腺癌患者死亡的重要因素，近年来越来越受关注，我们回顾性分析临床数据，发现乳腺癌患者心包钙化与肺转移不良预后正相关，此现象和机制未见报道。心包钙化导致心包纤维层变硬增厚，限制心脏舒张和静脉血回流，引起心脏功能障碍，心包切除术是唯一治疗手段，耗时长、恢复慢、死亡率高将限制其对乳腺癌患者心包钙化的治疗。我们初步发现，乳腺癌细胞可能通过分泌天冬酰胺内肽酶（AEP）促进Dermo1阳性细胞在小鼠心包组织定植和成骨分化导致心包钙化，分化中的Dermo1阳性细胞正反馈调节乳腺癌细胞的增殖、侵袭和转移。本项目我们将研究乳腺癌小鼠心包微环境的细胞类群及其时空变化特征、AEP促进Dermo1阳性细胞在心包组织定植和分化的机制，以及靶向抑制AEP信号通路对于改善小鼠心脏功能和乳腺癌预后的作用。本项目以“从解释临床现象到探索解决临床问题”为思路设置研究内容，具备科学研究意义和潜在应用价值。

Cardiovascular complication is an important factor in the death of patients with early breast cancer. In recent years, it has received mounting number of attention. We retrospectively analyzed clinical data and found that breast cancer patients' pericardial calcification is positively correlated with poor prognosis of lung metastasis. However, this phenomenon and mechanism have not been reported. Pericardial calcification leads to hardening and thickening of the pericardial fibrous layer, restricting cardiac diastole and venous blood return, and then causing cardiac dysfunction. Pericardectomy is the only treatment. Unfortunately, time-consuming, slow recovery, and high mortality will limit its application in pericardial calcification treatment of breast cancer patients. We initially found that breast cancer cells may promote the colonization and osteogenesis of Dermo1-positive cells in mouse pericardial tissue by secreting asparagine endopeptidase (AEP), leading to pericardial calcification. Dermo1-positive cells in differentiating give positive feedback regulation to proliferation, invasion and metastasis of breast cancer cells. In this project, we will investigate the cell groups in the pericardial microenvironment and their spatiotemporal changes, the mechanism of AEP promoting the colonization and differentiation of Dermo1 positive cells in pericardial tissue, and the targeted inhibition of the AEP signaling pathway for improving cardiac function and prognosis in the breast cancer mice. This project sets the research content following a certain line of "from explaining clinical phenomena to exploring and solving clinical problems", which has scientific research significance and potential application value.