| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2005: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
1.In the present study, the inhibition of expression and function of the Ca-activated K channel (IKca) in its involvement in vascular inflammation and subsequent vascular remodeling formation such as cell multiplication and dedifferentiation were investigated as therapeutic targets for vascular lesion formation.
2.Analysis of the molecular mechanism of IKca expression control in vascular smooth muscle cells and immune system cells. In order to determine the association between vascular lesion formation in states of cardiovascular disease characterized mainly by hypertension and arteriosclerosis, and IKca expression modification in vascular and immune cells, while also analyzing the possibility of IKca as a new therapeutic target, the following additional investigations were conducted in succession: a) analysis of the molecular mechanism of IKca expression control in vascular smooth muscle cells and immune cells, b) the search for a therapeutic drug that targeted IKca expression in the b
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ase clinical state model of vascular disease.
3.Cultured vascular smooth muscle cells from the rat aorta, obtained using the explant method, were cultured under stimulation by angiotensin II and PDGF, for analyses of the association between the expression of BTEB2 and of IKca occurring with phenotype transformation into the proliferative form, and the effects of NO donors and superoxide anions on IKca expression. Increases in BTEB2 and IKca expression were decreased by NO donors and intensified by superoxide anions. The search for a therapeutic drug that targets IKca expression in the base clinical state model of vascular disease
4.The relationship between the NFk-B activator, which is a transcription factor sensitive to redox as well as increased superoxide anion production resulting from NO decrease and has a corresponding site on IKca promoters, and IKca expression in smooth muscle and T-lymphocytes was discussed with respect to rats receiving prolonged L-NAME administration. In addition, as indicators for the inhibition of IKca expression and NFkB activation, the efficacies of the following were analyzed: (1) imidazole/pyrazole-type drugs, clotrimazole, TRAM34 (all are selective IKca inhibitors), (2) statin-type drugs, and (3) NS1619. Although all drugs tended to inhibit IKca expression and NFkB activation, no significant differences were observed. (4) The effect of low-molecular-weight heparin, which possesses antiplatelet and anti-inflammatory properties, was investigated using rats that received prolonged L-NAME administration. Low-molecular-weight heparin inhibited the cardiovascular remodeling that occurs with prolonged L-NAME administration, such as pericoronary fibrosis and increased medial smooth muscle hypertrophy. Less
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