新型脂肪因子FAM19A5调控血管稳态与重构的分子机制

脂肪组织对血管的稳态与重构起到重要的调控作用，脂肪因子是脂肪组织调控血管功能的重要介质，目前对于心血管保护作用的脂肪因子还知之甚少。我们前期工作发现了一种新型脂肪因子FAM19A5，肥胖时下调，并初步鉴定出其受体S1PR2。进一步预实验结果提示FAM19A5可能通过受体S1PR2，维持血管平滑肌细胞收缩表型及促进内皮修复。我们提出假说：FAM19A5-S1PR2轴通过对血管平滑肌细胞表型及内皮细胞修复的调控作用，维持血管稳态，抑制损伤后重构。我们拟通过细胞和在体水平研究FAM19A5在正常和肥胖状态下脂肪组织中的调控机制；利用不同的血管疾病模型在体明确脂肪来源的FAM19A5对血管稳态和重构的调控作用；深入探索FAM19A5-S1PR2信号转导的调控机制。通过本课题，我们拟发现脂肪调控血管稳态与重构的新的关键介质，为肥胖相关血管疾病的诊治提供新靶点。

Adipose tissue plays an important role in the regulation of vascular homeostasis and remodeling. Adipokines are the important mediators of adipose tissue-regulated vascular function. At present, little is known about the cardiovascular protective adipokines. In our previous work, we discovered a novel adipokine, FAM19A5, which was down-regulated during obesity, and initially identified its receptor S1PR2. Further preliminary results suggested that FAM19A5 may maintain the contractile phenotype of vascular smooth muscle cells and promote endothelial recovery through the receptor S1PR2. We hypothesized that the FAM19A5-S1PR2 axis maintains vascular homeostasis and inhibits post-injury remodeling by regulating the vascular smooth muscle cell phenotype and endothelial cell repair. We intend to study the regulation mechanism of FAM19A5 in adipose tissue under normal and obese conditions at in vitro and in vivo levels; to use different vascular disease models to clarify the regulation of vascular homeostasis and remodeling by adipose-derived FAM19A5; to explore the molecular mechanism of FAM19A5-S1PR2 signal transduction. Through this project, we intend to discover a novel critical mediator of adipose tissue-regulated vascular homeostasis and remodeling, and a potential target for the diagnosis and therapy of obesity-related vascular diseases.