Cell biological study on the genetic contribution in human atherosclerosis

建立高血压心血管并发症的评估方法是非常重要的。非侵入性评估对于高血压患者是必要的，因为这些患者的护城河没有临床症状。反应性充血和脉搏波速度分别是评价血管内皮功能和动脉僵硬的有用方法。此外，我们还引入了动脉僵硬指数，该指数是用计算机振荡法测量和计算的。这种方法和PWV一样方便实用。经胸多普勒记录冠状动脉左前降支的舒张期血流速度是研究心脏微循环的另一种新方法，它依赖于血管狭窄、内皮功能和血管僵硬。冠脉血流储备被定义为充血(由腺苷注射引起)与基础平均冠脉峰值血流速度的比率。对这些…的候选基因进行了遗传分析高血压心血管并发症的更直接的表型。我们分析了β3肾上腺素能受体作为交感神经活性的标志，8-OHdG DNA糖基化酶(HOGG1)作为氧化应激的标志，脂联素作为代谢综合征的候选者，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者。据报道，这些候选分子中的一些相互作用会导致动脉粥样硬化。我们正在进行的研究表明，这些相互作用中的一些可以通过基因基因相互作用来解释，即候选基因的一些多态性与其他分子的功能差异有关。我们还开发了一个分析系统来研究一个新的蛋白质的功能，该蛋白质将被我们的功能基因组方法鉴定，COS-1细胞中的Klotho蛋白表达系统就是一个模型。Klotho基因导入的COS-1细胞条件培养液可引起血管内皮细胞c-AMP和Mn-SOD的激活，进一步结合这两种方法进行功能遗传学检测将继续开拓血管医学新的临床应用前景

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