心肌纤维化是导致心肌梗死患者预后不良的主要原因。如何有效干预心肌纤维化是心血管研究领域的关键科学问题。成纤维细胞作为细胞外基质的主要生产者，在心肌纤维化过程中发挥重要作用，但其分子生物学机制尚未完全揭示。本项目前期工作发现心梗后心脏组织含黄素单氧化酶2（FMO2）含量显著降低，进一步研究显示FMO2主要由成纤维细胞表达。FMO2干扰慢病毒经心肌注射可下调心脏成纤维细胞FMO2表达，导致心功能受损，胶原沉积增加，肌成纤维细胞数量增多，并伴有TGFβ1/Smad3通路激活，提示FMO2可能在成纤维细胞调控心肌纤维化过程中扮演重要角色。因此，本项目拟在前期工作基础上，采用多种分子生物学手段和转基因动物模型，系统评价成纤维细胞FMO2对心肌纤维化的影响及作用方式，深入探讨FMO2调控成纤维细胞表型转化的信号通路，从新的角度阐明成纤维细胞参与心肌纤维化的分子机制，为心梗后心肌纤维化提供潜在干预靶点。

Cardiac fibrosis is a major cause of cardiac dysfunction and poor prognosis post myocardial infarction (MI). How to effectively manipulate cardiac fibrosis is a key scientific issue in the field of cardiovascular research. Recent studies show that fibroblasts are the predominant cell type in the adult heart, are the principal producers of extracellular matrix (ECM), and contribute largely to cardiac fibrosis. However, the detailed molecular mechanism is still unknown. Our preliminary study showed that the expression of cardiac flavin containing monooxygenase-2 (FMO2) is significantly reduced after myocardial infarction and FMO2 is mainly expressed by fibroblast. Intramyocardial injection with FMO2 shRNA lentivirus can down-regulate the expression of FMO2 in cardiac fibroblast, induce cardiac dysfunction and collagen accumulation, as well as TGFβ1/Smad3 signal pathway activation, indicating that fibroblast FMO2 may play an important role in cardiac fibrosis. Therefore, based on our previous work, our project will evaluate the effect of cardiac fibroblast FMO2 on post MI fibrosis and investigate the signal pathway of fibroblast phenotype transformation mediated by FMO2 using multiple molecular biological methods and transgenic animal models. The aim of our project is to clarify a novel mechanism of cardiac fibrosis regulated by fibroblast and provide potential intervention targets for cardiac fibrosis treatment.