CTRP1在肥胖加重血管稳态失衡中的作用和机制研究

Obesity is an independent risk factor for cardiovascular diseases. Recently, increasing studies suggest that adipose tissue exerts its systemic regulatory functions by secreting adipokines. However, the existence of the adipokine that promotes vascular injury is still unclear. In the present study, we showed that CTRP1 was mainly expressed by visceral adipose tissue. Serum level of CTRP1 was positively correlated with body mass index. Furthermore, we showed that CTPR1 leads to disturbed vascular homeostasis by impairing normal vascular functions, promoting vascular injury, and inhibiting mechanisms that repair the injury. In our next step, we will investigate the specific role of CTRP1 in regulating adipose inflammation and vascular homeostasis by using CTRP1 knockout mice and CTRP1 transgenic mice. We will further confirm the pivotal role of CTRP1 in linking obesity-induced adipose inflammation and disturbed vascular homeostasis by adipose tissue transplantation. We believe our study will aid the design of new strategies in clinical practice to reduce obesity-related cardiovascular events in early stage.

肥胖是心血管疾病的独立危险因素。近年的研究表明，脂肪组织能分泌具有生物活性的脂肪因子，参与机体多种功能调节，但是否存在介导血管损伤的脂肪因子并不清楚。我们的研究显示，CTRP1主要由内脏脂肪表达和分泌，其血清水平与肥胖程度呈正相关。进一步研究提示，CTRP1一方面参与了肥胖介导的脂肪炎症，另一方面则通过内分泌和旁分泌途径，抑制血管舒张功能、加重血管损伤、阻断修复机制，从而推动血管稳态失衡和血管重构的进展。我们下一步将利用CTRP1基因敲除和转基因小鼠，详细阐述CTRP1在介导脂肪炎症和血管稳态失衡中所扮演的角色。我们还将完善机制探讨，并利用异体脂肪移植进一步验证CTRP1在脂肪-血管轴调控的重要关联作用，为早期预测和干预以减少肥胖患者的心血管事件提供重要的靶点和途径。

肥胖是心血管疾病的独立危险因素。脂肪组织本身可分泌多种脂肪细胞因子（简称脂肪因子），调节局部和全身的炎症反应水平。本课题组通过前期蛋白组学筛选，鉴定出新脂肪因子CTRP1，首次发现：1）CTRP1是主要由脂肪组织分泌，促炎、促血管损伤的重要脂肪因子；2）CTRP1参与脂肪炎症和脂肪细胞分化；3）CTRP1是通过脂肪-血管轴发挥血管稳态调节作用的重要媒介；4）通过生物学手段干预CTRP1可明显减轻肥胖诱导的动脉粥样硬化发生发展。该研究为代谢性心血管疾病探索了新机制，提供了新的靶点，推动了诊疗优化。受本项目资助，本人已发表SCI论文12篇，累计影响因子58.7分；先后获上海市青年科技启明星计划、上海市卫生计生系统优秀青年医学人才培养计划；作为主要完成人先后获得上海市科技进步二等奖、教育部科技进步二等奖等奖项，并多次赴美国心脏协会（AHA）、欧洲心脏学会（ESC）、欧洲动脉粥样硬化学会（EAS）年会汇报相关学术成果。