Role of a novel visceral-derived endocrine factor in the development of atherosclerosis.

一种新型内脏源性内分泌因子在动脉粥样硬化发展中的作用。

基本信息

批准号：
13671155
负责人：
KIHARA Shinji
金额：
$ 2.3万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671155/
关键词：
atherosclerosis visceral fat visfatin endothelial cell monocyte chemotactic protein tumor necrosis factor macrophage coronary artery disease Visceroadipotropin

项目摘要

Obesity, defined as excess fat accumulation, is the most common cause of atherosclerotic cardiovascular morbidity and mortality in Japan. We have reported that intra-abdominal visceral fat accumulation due to overnutrition and physical inactivity is the common clinical background in the development of atherosclerosis. Based on the findings, we performed a differential display of visceral and subcutaneous fat tissue cDNA libraries, and found visceroadipotropin (renamed to visfatin), a novel secretory protein highly expressed in visceral fat tissue. The visfatin mRNA level was significantly higher in viscerl fat tissue compared with that in subcutaneous fat tissue. The recombinant visfatin protein enhanced the differentiation of adipocyte, suggesting that the molecule contributes to the visceral fat accumulation. In vitro experiments revealed that the recombinant protein stimulated the secretion of monocyte chemotactic protein-1 in the vascular endothelial cells, and tumor necrosis factor-alpha in the monocyte-derived macrophages. Consequently, we are studying the molecular mechanism in the development.of atherosclerosis through endocrine system. In clinical study, the plasma visfatin levels were significantly higher in patients with coronary artery disease (CAD) compared with those in control subjects. Currently, we are enrolling CAD patients to elucidate the clinical significance of this molecule. These results suggest that visfatin contributes to the visceral fat accumulation; and the measurement of the plasma level is helpful to evaluate the CAD risk.

肥胖被定义为过多的脂肪堆积，是日本动脉粥样硬化性心血管疾病发病和死亡的最常见原因。我们报道过，由于营养过剩和缺乏身体活动而导致的腹内内脏脂肪堆积是动脉粥样硬化发展的常见临床背景。基于这些发现，我们对内脏和皮下脂肪组织cDNA文库进行了差异展示，发现了内脏脂肪组织中高表达的新型分泌蛋白visceroadipotropin（更名为visfatin）。内脏脂肪组织中内脏脂肪素 mRNA 水平显着高于皮下脂肪组织。重组内脂素蛋白增强了脂肪细胞的分化，表明该分子有助于内脏脂肪的积累。体外实验表明，重组蛋白刺激血管内皮细胞分泌单核细胞趋化蛋白-1，以及单核细胞来源的巨噬细胞分泌肿瘤坏死因子-α。因此，我们正在通过内分泌系统研究动脉粥样硬化发生的分子机制。在临床研究中，冠状动脉疾病（CAD）患者的血浆内脂素水平显着高于对照组。目前，我们正在招募 CAD 患者来阐明该分子的临床意义。这些结果表明内脏脂肪素有助于内脏脂肪的积累；血浆水平的测量有助于评估CAD风险。