脂肪细胞来源Microparticles介导新生血管生成在2型糖尿病易损斑块形成中的作用

项目名称： 脂肪细胞来源Microparticles介导新生血管生成在2型糖尿病易损斑块形成中的作用

项目编号： No.81470560

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 钟明

作者单位： 山东大学

项目金额： 73万元

中文摘要： 病理性新生血管是动脉粥样硬化易损斑块形成的重要机制，炎症又是斑块内血管新生的核心驱动因素，脂肪组织炎症是糖尿病动脉粥样硬化形成的根源之一。Microparticles（微粒）是脂肪组织与血管间信息传递的重要载体，但是脂肪组织能否通过释放Microparticles 架起脂肪组织炎症和病理性新生血管生成之间的桥梁,促进易损斑块形成尚不清楚。我们前期研究表明脂肪来源的Microparticles（ADM）携带大量的促血管生成因子Hedgehog蛋白。因此，我们提出脂肪组织是通过Microparticles及其携带的Hedgehog蛋白架起了糖尿病状态下脂肪组织炎症和病理性新生血管生成之间桥梁的研究计划。本课题拟在细胞、动物和临床患者标本3个层面，深入探讨ADM介导的Hedgehog信号通路促进病理性新生血管生成，进而影响糖尿病易损斑块形成的机制。研究结果将为糖尿病大血管并发症的防治提供新的靶点

中文关键词： 动脉粥样硬化；易损斑块；血管新生；微粒；脂肪组织

英文摘要： Pathological neoangiogenesis has a pivotal role in the progression of vulnerable atherosclerotic plaques, and inflammation represents a critical causal factor promoting intraplaque neoangiogenesis. Adipose tissue inflammation is one of the underlying causes of diabetic atherosclerosis. Microparticles are important transport vehicle between adipose tissue and blood vessels. However, it still remains unclear whether microparticles released from adipose tissue can build a bridge between adipose tissue inflammation and pathological neoangiogenesis promoting progression of atherosclerotic plaques. Our previous studies have shown that adipocyte-derived microparticles (ADM) carried large amounts of pro-angiogenic factor Hedgehog protein. Therefore, we hypothesize that adipose tissue may build a bridge between adipose tissue inflammation and pathological neoangiogenesis in diabetes via ADM harboring Hedgehog protein. At levels of cell, animal and clinical specimens from patients, we aim to conduct systematic and in-depth exploration of the mechanism by which Hedgehog signaling pathway mediated by ADM promote neoangiogenesis and further effect the progression of diabetic vulnerable plaques. These results may provide new targets for prevention and cure of macrovascular complications of diabetes.

英文关键词： Atherosclerosis;Vulnerable Plaque;Neoangiogenesis;Microparticles;Adipose Tissue