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Cell biological study on the genetic contribution in human atherosclerosis

关于人类动脉粥样硬化遗传贡献的细胞生物学研究

基本信息

批准号：
13670709
负责人：
RAKUGI Hiromi
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-13670709/
关键词：
atherosclerosis gene polymorphism pulse wave velocity vascular endothelial function hypertension 脳波速度

项目摘要

It is important to develop the methods for assessment of cardiovascular complications by hypertension. Non-invasive assessment is essential for hypertensive subjects because moat of those patients have no clinical symptoms. Reactive hyperemia and pulse wave velocity are useful methods to evaluate endothelial function and arterial stiffness, respectively. Furthermore, we introduced arterial stiffness index which was measured and calculated by computerized oscillometry. This method is very convenient and useful as well as PWV. Transthoracic Doppler recording of diastolic coronary flow velocity in the left anterior descending coronary artery is another new approach to investigate cardiac microcirculation which depends on vascular stenosis, endothelial function and vascular stiffness. Coronary flow reserve was defined as the ratio of hyperemic (induced by adenosine infusion) to basal averaged peak coronary flow velocity.Genetic analysis of candidate genes have been performed for these inte … More rmediate phenotypes of hypertensive cardiovascular complications. We analyzed Beta3 adrenergic receptor as a marker of sympathetic activity, 8-OHdG DNA glycosylase (hOGG1) as a marker of oxidative stress, adiponectin as a candidate of metabolic syndrome, and MCP-1, CC chemokine receptor 2, interleukin-15, and ICMA-1 as candidates of inflammation related atherosclerosis. It has been reported that some of these candidate molecules interact each other to develop atherosclerosis. Our ongoing studies have shown that some of these interactions can be interpreted a part by gene gene interaction, that is, some polymorphisms of candidate genes associated with functional differences of other molecule.We also developed the analyzing system to investigate the function of a novel protein which would be identified by our functional genomic approach, Klotho protein expression system in COS-1 cells is a model of it. Conditioned medium of klotho gene-introduced COS-1 cells caused c-AMP activation and Mn-SOD activation in endothelial cells.Further examinations of functional genetics by combination of these methods is continued to develop a new clinical applications in vascular medicine Less

因此，建立高血压心血管并发症的评价方法具有重要意义。高血压患者大多无临床症状，无创性评估是必要的。反应性充血和脉搏波速度分别是评价内皮功能和动脉硬度的有用方法。此外，我们还介绍了动脉硬化指数的测量和计算的计算机化的血管造影术。该方法与PWV方法一样，使用方便，实用性强.经胸多普勒记录冠状动脉左前降支舒张期血流速度是研究心脏微循环的另一种新方法，心脏微循环取决于血管狭窄、内皮功能和血管硬度。冠状动脉血流储备被定义为充血（由腺苷输注诱导）与基础平均峰值冠状动脉血流速度的比值。 ...更多信息高血压心血管并发症的直接表型。我们分析了β 3肾上腺素能受体作为交感神经活性的标志物，8-OHdG DNA糖基化酶（hOGG1）作为氧化应激的标志物，脂联素作为代谢综合征的候选物，以及MCP-1、CC趋化因子受体2、白细胞介素-15和ICMA-1作为炎症相关动脉粥样硬化的候选物。据报道，其中一些候选分子相互作用而导致动脉粥样硬化。我们正在进行的研究表明，这些相互作用中的一部分可以通过基因间的相互作用来解释，即候选基因的某些多态性与其他分子的功能差异相关，我们还开发了分析系统来研究一种新蛋白的功能，该蛋白将通过我们的功能基因组学方法来鉴定，COS-1细胞中Klotho蛋白表达系统是一个模型，导入Klotho基因的COS-1细胞的条件培养液引起c-AMP激活和Mn-2的释放，内皮细胞中SOD的激活。通过这些方法的组合进一步检查功能遗传学，继续开发新的血管医学临床应用。