血管内皮功能紊乱是腹主动脉瘤（AAA）病理过程的关键环节，但发病机制尚未完全阐明。尿素通道B（UT-B）在血管内皮细胞表达，其基因敲除可阻止内皮细胞产生的尿素外排，抑制精氨酸酶表达和活性，增加eNOS活性，产生更多的NO，调节内皮功能。前期工作发现，UT-B敲除能减轻Ang II诱导的AAA动脉直径扩大和弹力板断裂，减少AAA血管炎症反应中巨噬细胞浸润和MMP表达。因此，提出科学假说“UT-B介导内皮细胞内尿素排出，其功能抑制可导致内皮细胞内尿素水平升高，进而上调eNOS的活性、NO水平及相关信号通路，减缓AAA发病过程”。本项目拟在UT-B基因敲除小鼠基础上建立Ang II诱导AAA模型，并应用牛主动脉细胞模型，给予UT-B特异性抑制剂，通过研究UT-B功能抑制状态下内皮细胞eNOS等信号通路变化，揭示UT-B在AAA发病过程中的作用，为发现防治AAA新的药物靶点提供实验数据和理论依据。

Endothelial dysfunction has been recognized as a critical step in the development of abdominal aortic aneurysm (AAA) formation. However, the molecular mechanisms underlying this process are not fully understood. Urea transporters B (UT-B) is a membrane protein expressed in vascular endothelial, and can selectively transport urea driven by a concentration urea gradient across cell membrane. UT-B deficiency prevents the secretion of urea. The accumulation of intracellular urea in turn inhibits the expression and activity of Arginase I, increases the expression of eNOS and p-eNOS, and then produced more nitric oxide, which was further involved in the regulation of endothelial function. Our preliminary data showed that, UT-B deficiency inhibited Ang II-induced increase in the maximal diameters of infrarenal abdominal aortas and elastin degradation related to AAA formation. At the same time, macrophage infiltration and matrix metalloproteinase (MMP) upregulation, which are important drivers of AAA by promoting inflammation and extracellular matrix remodeling, were downregulated in angiotensin II-treated UT-B deficient mice. In this study, by the use of an in vivo Ang II-induced AAA mouse model in UT-B deficient mice, and performing in vitro experiments using bovine aortic cells and UT-B specific inhibitor, we aimed to explore the role of UT-B in the formation AAA. We supposed that the changes of eNOS coupling, oxidative stress, inflammation and other signal pathways may be involved in this process. In summary, our study aimed to provide the experimental data and theoretical basis of the roles of UT-B in the formation of abdominal aortic aneurysm, which may further open up new opportunities for the development of new AAA therapeutic drugs.