Document Detail

Decreased cardiac mitochondrial tetrahydrobiopterin in a rat model of pressure overload.
MedLine Citation:
PMID:  23313998     Owner:  NLM     Status:  Publisher    
Sustained cardiac pressure overload induces mitochondrial dysfunction and apoptosis of cardiomyocytes leading to pathological cardiac hypertrophy and dysfunction. Mitochondrial nitric oxide synthase (NOS) appears to cause uncoupling, which produces reactive oxygen species (ROS) instead of nitric oxide (NO), by a decrease in the cofactor tetrahydrobiopterin (BH4). This study focused on examining the changes in mitochondrial BH4 levels during cardiac pressure overload. Chronic cardiac pressure overload was generated by abdominal aortic banding in rats. Levels of BH4 and its oxidized form were measured in the mitochondria isolated from the left ventricle (LV) and the post-mitochondrial supernatants. Chronic aortic banding increased blood pressure, and induced cardiac hypertrophy and fibrosis. Notably, the BH4 levels were decreased while its oxidized forms were increased in LV mitochondria, but not in the post-mitochondrial supernatants containing the cytosol and microsome. Anti-neuronal NOS antibody-sensitive protein was detected in the cardiac mitochondria. Moreover, continuous administration of BH4 to rats with pressure overload increased mitochondrial BH4 levels and reduced cardiac fibrosis and matrix metallopeptidase activity, but not cardiac hypertrophy. These findings show the possibility that NOS uncoupling by decreased cardiac mitochondrial BH4 levels is implicated, at least in part, in the development of cardiac fibrosis, leading to cardiac dysfunction induced by pressure overload.
Shunichi Shimizu; Masaaki Ishibashi; Sumito Kumagai; Teruaki Wajima; Toshihito Hiroi; Tatsuya Kurihara; Masakazu Ishii; Yuji Kiuchi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-10
Journal Detail:
Title:  International journal of molecular medicine     Volume:  -     ISSN:  1791-244X     ISO Abbreviation:  Int. J. Mol. Med.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9810955     Medline TA:  Int J Mol Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Pathophysiology, Showa University School of Pharmacy, Tokyo 142-8555, Japan.
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