主动脉旁脂肪细胞在血管紧张素II诱导的血管重构中作用及其机制

Aortic adipose tissue, consisting of multiple cell types, contributes to maintenance of normal aortic structure and regulation of physical funtion. Moreover, it plays a crital role of endocrine-immunology, which may participate in vascular remodeling. Angiotensin II (AngII), a bioactive octopeptide, is exsitent under normal physical conditions, which regulate cardiovascular development, functional homeostasis, electrolyte and fluid balance. Our previous studies have developed AngII-induced abdominal aortic aneurysm in hypercholesterolemic mice. The present study would establish AngII-induced aortic aneurysm mouse models and investigate the role of periaortic adipose tissue around accending aorta on aortic physical function and pathological remodeling (aortic dissection), mediated by the potential mechansims of inflammation and immune response. Furthermore, we would explore whether AngII alter intracellular transcription of RIP140 and PPAR-γ mRNA and secretion of adipokines and inflammatory cytokines by activating AT1a receptor on periaortic adipose tissue around accending aorta and then intracellular p38 MAPK signaling pathways, which contributes to vascular remodeling. The present studies helps to better understand the vascular physical adaptation and remodeling mechanism and figure out the therapeutic targets for patients suffered with aortic aneurysm, which may have scientific significance and social value.

主动脉旁脂肪组织含多种细胞成分，与血管正常结构和功能调节密切相关，兼具内分泌-免疫功能，可能参与血管重构过程。血管紧张素II是正常生理存在的八肽分子，调节着心血管系统发育、功能稳态、电解质和体液平衡。本项目利用血管紧张素II诱导主动脉瘤动物模型，研究升主动脉旁脂肪组织在主动脉生理功能和病理重构（主动脉夹层）中地位及可能通过旁分泌和免疫机制调节主动脉壁炎症状态，明确血管紧张素II经由升主动脉旁脂肪细胞膜AT1a受体激活细胞内p38MAPK信号转导通路，启动RIP140和PPAR-γ转录水平变化，促进脂肪因子和炎性因子分泌，参与主动脉壁重构。通过对主动脉旁脂肪组织在血管紧张素II诱导主动脉重构中的机制研究，有助于认识血管生理适应和病理重构机制，寻找可能的药靶，为临床主动脉瘤患者治疗提供可行性策略，具有重要科学意义和社会价值。

主动脉旁脂肪组织含多种细胞成分，与血管正常结构和功能调节密切相关，兼具内分泌-免疫功能，可能参与血管重构过程。血管紧张素II是正常生理存在的八肽分子，调节着心血管系统发育、功能稳态、电解质和体液平衡。本项目利用血管紧张素II诱导模型，研究发现血管紧张素II能诱导apoE-/-雄性小鼠发生腹主动脉瘤，同时可造成升主动脉弓扩张，主要通过AT1a受体介导发挥作用。血管紧张素II能诱导apoE-/-雄性小鼠腹主动脉旁脂肪组织AT1a受体表达上调和leptin表达下调，腹主动脉壁组织MCP-1等炎症指标增高，造成主动脉中层断裂和动脉瘤的形成。血管紧张素II通过上调apoE-/-雄性小鼠胸主动脉壁（升主动脉弓）AT1a受体，造成局部主动脉壁MCP-1和leptin表达增加，促进胸主动脉扩张。血管紧张素II应用后不发生腹主动脉瘤的小鼠中，腹主动脉旁脂肪组织AT1a受体上调和leptin表达下调，而腹主动脉壁组织resistin表达增加、MCP-1水平不增高。提示在血管紧张素II诱导的腹主动脉模型中，resistin可能在预防腹主动脉瘤的发生起重要作用。通过对主动脉旁脂肪组织在血管紧张素II诱导主动脉重构中的机制研究，有助于认识血管生理适应和病理重构机制，寻找可能的药靶，为临床主动脉瘤患者治疗提供可行性策略，具有重要科学意义和社会价值。