Posttranslational modifications in Marfan’s disease mediated by myeloperoxidase (A04+)

该项目旨在揭示先天性免疫系统在马凡综合征(MFS)中的作用，并将确定细胞外基质蛋白、基质降解酶和髓过氧化物酶(MPO)在MFS相关主动脉疾病中的相互作用。我们假设，渗入主动脉的先天免疫细胞通过产生MPO的能力促进疾病进展，MPO发挥强大的基质破坏稳定作用，并影响血管的结构完整性。一旦确定了因果关系，我们建议从药物上抑制MFS小鼠模型中的MPO，作为一种治疗主动脉疾病的新策略。

This project aims to uncover the role of the innate immune system in Marfan Syndrome (MFS) and will define the interplay between extracellular matrix proteins, matrix-degrading enzymes, and myeloperoxidase (MPO) in MFS-related aortic disease. We hypothesize that innate immune cells extravasating into the aorta contribute to disease progression by their capacity to produce MPO, which exerts potent matrix destabilizing effects and affects the structural integrity of the vessel. Once the causality has been established, we propose to pharmacologically inhibit MPO in murine models of MFS as a new therapeutic strategy against aortic disease.