Role of endothelial cell selective adhesion molecule (ESAM) in the genesis of diabetic vasculopathy

内皮细胞选择性粘附分子（ESAM）在糖尿病血管病变发生中的作用

• 批准号: 17590734
• 负责人: ISHIDA Tatsuro
• 金额: $ 2.24万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590734/
• 关键词: adhesion molecule; diabetes mellitus; endothelium; retinopathy; angiogenesis; atherosclerosis; diabetic vasculopathy; inlammation

1) Role of ESAM in diabetes mellitusEndothelial cell selective adhesion molecule (ESAM) is a new member of the immunoglobulin family adhesion molecule which has been cloned from vascular endothelial cells. ESAM expression is selectively restricted to vascular endothelial cells. To clarify the role of ESAM in the genesis of diabetic vasculopathy, aortic endothelial cells were isolated from wild-type and ESAM knockout mice and endothelial permeability was evaluated using the modified Boyden chamber system with the Evance Blue dye. The ESAM deficient endothelial cells showed a significant increase of endothelial cell permeability when compared to wild type endothelial cells. Consistent with this result, ESAM knockout mice showed marked albuminuria when compared to wild type mice. When wild type and ESAM knockout mice were injected with streptozotocin to evoke diabetes, ESAM knockout mice showed severer albuminuria and hypoalbuminemia. These results indicate that ESAM regulates endothelial permeability, and a decrease in ESAM expression increase the albuminuria. Thus, ESAM may play an important role in the pathophysiology of early stages of diabetic nephropathy by modulating glomerular permeability.2) Role of ESAM in atherosclerosisESAM knockout mice were bred with apoE knockout mice to generate the ESAM-apoE double knockout mice. Aortic atherosclerotic lesions were evaluated by Sudan III staining. Atherosclerotic lesion of ESAM-apoE double knockout mice were significantly smaller than the control apoE knockout mice. The macrophage content in the atherosclerotic lesion was smaller in ESAM-apoE double knockout mice than in apoE knockout mice. These results indicate that ESAM regulates the formation of atherosclerosis by modulating eodnthelial-hepatopoietic cell interaction.

1)ESAM在糖尿病中的作用内皮细胞选择性黏附分子(ESAM)是从血管内皮细胞克隆的免疫球蛋白家族的新成员。ESAM的表达选择性地局限于血管内皮细胞。为了阐明ESAM在糖尿病血管病变发生中的作用，从野生型和ESAM基因敲除小鼠分离主动脉内皮细胞，用改良的Boyden小室系统检测内皮通透性。与野生型内皮细胞相比，ESAM缺陷内皮细胞的通透性显著增加。与这一结果一致的是，ESAM基因敲除小鼠与野生型小鼠相比显示出显著的蛋白尿。当野生型和ESAM基因敲除小鼠注射链脲佐菌素诱发糖尿病时，ESAM基因敲除小鼠表现出更严重的蛋白尿和低蛋白血症。这些结果表明ESAM调节血管内皮细胞的通透性，ESAM表达的减少增加了蛋白尿。因此，ESAM可能通过调节肾小球通透性在糖尿病肾病早期的病理生理过程中发挥重要作用。2)ESAM在动脉粥样硬化中的作用苏丹红III染色评价动脉粥样硬化病变。ESAM-apoE双基因敲除小鼠的动脉粥样硬化病变明显小于对照apoE基因敲除小鼠。ESAM-apoE双基因敲除小鼠动脉粥样硬化病变内巨噬细胞含量明显低于apoE基因敲除小鼠。这些结果表明，ESAM通过调节内皮-肝细胞间的相互作用来调节动脉粥样硬化的形成。

项目成果

Endothelial urocortin has potent antioxidative properties and is upregulated by inflammatory cytokines and pitavastatin

• DOI: 10.1159/000090132
• 发表时间: 2006-01-01
• 期刊: JOURNAL OF VASCULAR RESEARCH
• 影响因子: 1.7
• 作者: Honjo, T;Inoue, N;Yokoyama, M
• 通讯作者: Yokoyama, M

Increased expression of endothelial lipase in rat model of hypertension.

高血压大鼠模型中内皮脂肪酶表达增加。

• 发表时间: 2005
• 期刊: Cardiovasc Res (in press)
• 作者: Kurata Y;et al.;Shimokawa Y
• 通讯作者: Shimokawa Y

New function of calreticulin: calreticulin-dependent mRNA destabilization.

• DOI: 10.1161/01.res.0000193564.46466.2a
• 发表时间: 2005-11
• 期刊: Circulation research
• 影响因子: 20.1
• 作者: M. Yokoyama;K. Hirata

Xenogenic smooth muscle cell immunization reduces neointimal formation in balloon-injured rabbit carotid arteries.

• DOI: 10.1016/j.cardiores.2005.06.016
• 发表时间: 2005-11
• 期刊: Cardiovascular research
• 影响因子: 10.8
• 作者: M. Shinohara;S. Kawashima;T. Yamashita;Tomofumi Takaya;R. Toh;T. Ishida;T. Ueyama;N. Inoue;K. Hirata;M. Yokoyama

Chylomicron remnants upregulate CD40 expression via the ERK pathway and a redox-sensitive mechanism in THP-1 cells

• DOI: 10.1016/j.atherosclerosis.2005.09.002
• 发表时间: 2006-08-01
• 期刊: ATHEROSCLEROSIS
• 影响因子: 5.3
• 作者: Kamemura, Kohei;Fujioka, Yoshio;Yokoyama, Mitsuhiro
• 通讯作者: Yokoyama, Mitsuhiro