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Effects of abnormal gene expression on accelerated atherosclerosis in Werner syndrome.

异常基因表达对维尔纳综合征加速动脉粥样硬化的影响。

基本信息

批准号：
07670515
负责人：
MURANO Shunichi
金额：
$ 1.41万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670515/
关键词：
Werner syndrome atherosclerosis pasminogen activator inhibitor-1 intercellular adhesion molecule-1 vascular cell adhesion molecule-1 Intercelular adhesion molecule-1 scavenger receptor fibronectin OLETFラット mitochondria acetylated LDL

项目摘要

Werner syndrome is a rare premature aging syndrome accompanied by severe atherosclerosis. The etiology of atherosclerosis is suspected to be due to its complications, namely diabetes mellitus, hyperinsulinemia and hyperlipidemia. But from an autopsy case we found that some other risk factors may be involving in the mechanism of atherosclerosis in this syndrome. Previously we revealed that pasminogen activator inhibitor-1 (PAI-1) gene was being overexpressed in skin fibroblasts from a patient with this syndrome. PAI-1 is a potent inhibitor of tissue plasminogen activator and a possible risk factor of atherosclerosis. This led us to assess the plasma concentration of PAI-1. Our working hypothesis was that PAI-1 gene was upregulated or not fully suppressed in cells responsible for the production of PAI-1 in plasma as well as in fibroblasts. The result shown a high concentration of plasma PAI-1. One of well-known physiological substances that induce the PAI-1 gene is tumor necrosis factor-alpha (TNF-alpha), which also induces other possible risk factors of atherosclerosis, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1. We found the serum concentration of ICAM-1 to be elevated in patients with this syndrome. We conclude that high concentration of PAI-1 and ICAM-1 in blood may be one of the potent causes of severe atherosclerosis in Werner syndrome.

Werner综合征是一种罕见的伴有严重动脉粥样硬化的早衰综合征。动脉粥样硬化的病因被怀疑是由于其并发症，即糖尿病，高胰岛素血症和高脂血症。但从尸检病例中我们发现，其他一些危险因素可能参与了该综合征动脉粥样硬化的发生机制。先前，我们发现，纤溶酶原激活物抑制剂-1（派-1）基因被过度表达在皮肤成纤维细胞从这种综合征患者。派-1是组织纤溶酶原激活物的有效抑制剂，可能是动脉粥样硬化的危险因素。这导致我们评估派-1的血浆浓度。我们的工作假设是，派-1基因上调或不完全抑制细胞负责生产派-1的血浆以及成纤维细胞。结果表明，血浆派-1浓度较高。众所周知，诱导派-1基因的生理物质之一是肿瘤坏死因子-α（TNF-α），其还诱导动脉粥样硬化的其他可能的危险因子，细胞间粘附分子-1（ICAM-1）和血管细胞粘附分子-1。我们发现，ICAM-1的血清浓度升高，在这种综合征的患者。提示派-1和ICAM-1在Werner综合征中的高浓度表达可能是导致严重动脉粥样硬化的重要原因之一。