Cell biological study on the genetic contribution in human atherosclerosis

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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