Elucidation of mechanism of chronic inflammation originated from mitochondria, and the application for the treatment of heart failure

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We elucidated that mitochondrial DNA plyas important role in the onset of chronic inflammation, which is regarded to cause heart failure. We observed that mitochondrial DNA results from inadequate degradation by autophagy, and the key molecule for mitochondrial DNA degradation is DNase II, a lysosomal enzyme. Resultant mitochondrial DNA in cardiomyocytes upregulates the expression of inflammatory cytokines mediated through toll like receptor 9 (TLR9). Inhibition of interection between mitochondrial DNA and TLR9 suppressed the development of heart failure in response to pressureoverload. These findings indicate that the inhibition of TLR9 activation by mitochondrial DNA may be the treatment of patients with heart failure.