Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Outline of Final Research Achievements |
Inositol trisphosphate receptor (IP3R) is an intracellular Ca2+ release channel. As we found the strong expression of the type 2 IP3R (IP3R2) in the pulmonary arterial smooth muscle cells (PASMCs), we investigated the contribution of IP3R2 to pathophysiology of PAH. IP3R2 knockout (KO) mice treated with chronic hypoxia showed higher PA pressure and RV pressure than WT mice in echocardiography. RV hypertrophy and medial wall thickness of PASMCs were more severe in KO. There was significant decrease of TUNEL positive cells in KO, suggesting that apoptosis was reduced in KO PASMCs. Ca2+ imaging revealed that SOCE was enhanced in KO compared with WT. Taken together, chronic hypoxia-induced PAH was deteriorated in IP3R2 KO. The deletion of IP3R2 gene led to inhibition of apoptosis and enhanced SOCE in PASMCs, probably resulting in acceleration of the progression of PAH induced by chronic hypoxia.
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