血管周围脂肪组织通过脂肪因子CTRP5促进主动脉瘤发生及其机制研究

Periaortic adipose tissue, because of its contiguity to the aorta, may promote vascular remodeling and aortic dilatation. By using RNA deep sequencing analyses, we found the expression of CTRP5 was increased in the periaortic adipose tissue of the aortic aneurysm. CTRP5, a member of C1q/TNF related protein (CTRP) family, is a novel secreted glycoprotein and its biological functions are largely undefined. To investigate whether CTRP5 is involved in the pathophysiological process of aortic aneurysm and its function, we established CTRP5 knockout mice and abdominal aortic aneurysm (AAA) model induced by angiotensin II. Compared with single Apoe gene knockout mice, Apoe/Ctrp5 double knockout mice infused with angiotensin II had significantly reduced incidence of abdominal aortic aneurysm, inflammatory cell infiltration and aortic expansion. In vitro experiments showed that CTRP5 secreted by adipose tissue increased the secretion of pro-inflammatory cytokines and migration of monocytes/macrophages. To further study the function of CTRP5 in the interaction of periaortic adipose tissue and aortic aneurysm, we established the periaortic adipose tissue transplant model and found that CTRP5 knockout in the periaortic adipose tissue was less likely to result in aneurysm formation and aortic wall inflammation compared with the wild-type transplantation group. In our future experiments, we will test this hypothesis in vitro and in vivo and to elucidate the specific molecular mechanisms.

主动脉周围脂肪由于与主动脉毗邻，可促进血管重构和主动脉扩张。通过转录组测序分析，我们发现脂肪因子CTRP5在动脉瘤周围脂肪组织中表达增加。CTRP5是一种新型的分泌糖蛋白，其生物学功能尚未明确。为了研究CTRP5在动脉瘤病理发生中的作用，我们建立了CTRP5基因敲除小鼠及血管紧张素II诱导的腹主动脉瘤模型，发现与Apoe基因单敲除小鼠相比，Apoe/Ctrp5基因双敲除小鼠腹主动脉瘤发生率显著减少，血管壁炎性细胞浸润及主动脉扩张降低。体外实验显示，脂肪组织可通过分泌CTRP5增加促炎细胞因子分泌和单核巨噬细胞迁移。我们进一步建立了主动脉周围脂肪组织移植模型，证实移植了CTRP5基因敲除血管周围脂肪组织的受体小鼠较野生型移植组相比，动脉瘤发生和血管壁炎症显著减少。我们下一步将在体外和体内验证这一假说，并阐明具体的分子发生机制。

主动脉周围脂肪不仅仅是血管的一种结构支撑，它可以分泌多种生物活性物质，在调节血管功能中起重要作用。我们通过比较正常血管周围脂肪组织及主动脉瘤周围脂肪组织的基因表达谱，发现脂肪因子CTRP5在病变血管周围脂肪组织表达增高。为了研究CTRP5在动脉瘤病理发生中的作用，我们建立CTRP5基因敲除小鼠及血管紧张素II诱导的腹主动脉瘤模型，发现与Apoe基因单敲除小鼠相比，Apoe/Ctrp5基因双敲除小鼠腹主动脉瘤发生率显著减少，血管壁炎性细胞浸润及主动脉扩张降低。进一步建立了主动脉周围脂肪组织移植模型，证实移植了CTRP5基因敲除血管周围脂肪组织的受体小鼠较野生型移植组相比，动脉瘤发生和血管壁炎症显著减少。体外实验进一步显示，脂肪组织可通过分泌CTRP5增加促炎细胞因子分泌和单核巨噬细胞迁移，促进动脉瘤的发生发展。