| Budget Amount *help |
¥26,650,000 (Direct Cost: ¥20,500,000、Indirect Cost: ¥6,150,000)
Fiscal Year 2011: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Fiscal Year 2010: ¥19,240,000 (Direct Cost: ¥14,800,000、Indirect Cost: ¥4,440,000)
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| Research Abstract |
Structural remodeling of the heart induced by chronic hypertension or ischemia is a major cause for cardiac dysfunction. We have previously reported that diacylglycerol-activated transient receptor potential canonical channels(TRPC3 and TRPC6) mediate pressure overload-induced cardiac hypertrophy invivo. We here focused on the fact that TRPC6 channel activities are negatively regulated by Thr69 phosphorylation, and found that inhibition of PDEs or atrial natriuretic peptide suppresses cardiac hypertrophy and hypertension through TRPC6 inhibition. Notably, TRPC6 proteins formed a protein signaling complex with PKA and PDE3 in vascular smooth muscle cells. Furthermore, TRPC3 interacts with protein kinase C dependently on TRPC3-mediated Ca2+ influx, leading to production of reactive oxygen species via activation of NADPH oxidase, resulting in development of cardiac remodeling, such as hypertrophy and fibrosis. These results strongly suggest that formation of TRPC3/6 protein signaling complex plays a pivotal role in cardiac remodeling.
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