| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 2005: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Research Abstract |
1 Mast cells are multi-potent inflammatory cells, which express numerous bioactive factors, such as cytokines, growth factors, and proteases. Mast cells are known to locate in cardiovascular tissues. However, the role of mast cells on the pathogenesis of cardiovascular disease is unknown.
2 Our present study attempted to clarify the role of mast cells by analyzing spontaneously hypertensive rats (SHR), which is known to develop genetically hypertension, cardiac hypertrophy, and heart failure.
3 Histochemical analysis revealed that the number of mast cells in the cardiovascular tissues of prehypertensive (2 weeks-old) SHR was significantly higher than that of normal control WKY rats, and mast cells are one of the major cells producing TNF-alpha and chymase. Furthermore, TNF-alpha,NF-kB,IL-6,SCF and c-kit mRNA levels in the cardiovascular tissues in SHR were higher than those in WKY rats.
4 To further investigate the role of mast cells in SHR, we evaluated the therapeutic effects of a mast cell stabilizer, tranilast, on the development of hypertension in SHR. Montelukast (300 mg/kg/day) was orally administered to SHR for 10 weeks, starting at the age of 2 weeks.
5 Treatment with tranilast significantly inhibit the development of hypertension, and decreased the number of mast cells in cardiovascular tissues in SHR. Tranilast also suppressed the perivascular fibrosis and vascular thickening.
6 In conclusion, our results support the hypothesis that activation of mast cells in cardiovascular tissues may play a key role in the pathogenesis of cardiovascular diseases.
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