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

1)内皮细胞选择性粘附分子（Endothelial cell selective adhesion molecule，ESAM）是从血管内皮细胞中克隆的免疫球蛋白家族粘附分子的新成员。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敲除小鼠中分离主动脉内皮细胞，并使用具有Evance Blue染料的改良Boyden室系统评价内皮渗透性。与野生型内皮细胞相比，ESAM缺陷型内皮细胞显示出内皮细胞通透性的显著增加。与该结果一致，当与野生型小鼠相比时，ESAM敲除小鼠显示出显著的白蛋白尿。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调节内皮通透性，ESAM表达的减少增加白蛋白尿。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学中发挥重要作用。2）ESAM在动脉粥样硬化中的作用ESAM基因敲除小鼠与apoE基因敲除小鼠交配，产生ESAM-apoE双基因敲除小鼠。苏丹III染色评价主动脉粥样硬化病变。ESAM-apoE双基因敲除小鼠的动脉粥样硬化病变明显小于对照组。ESAM-apoE双基因敲除小鼠动脉粥样硬化病变中的巨噬细胞含量小于apoE基因敲除小鼠。这些结果表明，ESAM通过调节内皮细胞-肝细胞相互作用来调节动脉粥样硬化的形成。

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.