2013 Fiscal Year Final Research Report

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

Research Project

Project/Area Number	23689042
Research Category	Grant-in-Aid for Young Scientists (A)
Allocation Type	Single-year Grants
Research Field	Circulatory organs internal medicine
Research Institution	Osaka University
Principal Investigator	HIKOSO Shungo 大阪大学, 医学部附属病院, 特任准教授(常勤) (30423164)
Project Period (FY)	2011-04-01 – 2014-03-31
Keywords	分子心臓病態学
Research Abstract	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 pressure overload. These findings indicate that the inhibition of TLR9 activation by mitochondrial DNA may be the treatment of patients with heart failure.