Document Detail


eNOS correlates with mitochondrial biogenesis in hearts of congenital heart disease with cyanosis.
MedLine Citation:
PMID:  22858618     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Mitochondrial biogenesis program in heart appears to exhibit adaptive remodeling following biomechanical and oxidative stress. The adaptive mechanisms that protect myocardium metabolism during hypoxia are coordinated in part by nitric oxide (NO).
OBJECTIVE: To observe mitochondrial biogenesis and nitric oxide synthase (NOS) expression in hearts of congenital heart disease with cyanosis, discuss mitochondrial response to chronic hypoxia in myocardium.
METHODS: 20 patients with cyanotic (n=10) or acyanotic cardiac defects (n=10) were investigated. Samples from the right ventricular outflow tract myocardium taken during operation were studied. Morphometric analysis of mitochondria was performed with transmission electron microscope. Relative mtDNA/nDNA ratio was determined with real-time PCR. Cytochrome c oxidase subunit I (COXI), peroxisome-proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (Tfam) transcript levels were detected by real-time fluorescent RT-PCR. COXI and nNOS, iNOS and eNOS protein levels were measured with western blot.
RESULTS: Mitochondrial volume density (Vv) and numerical density (Nv) were significantly elevated in patients with cyanotic compared to acyanotic congenital heart disease. Elevated mtDNA and up-regulated COXI, PGC-1α, NRF1 and Tfam mRNA levels were observed in cyanotic patients. Protein levels of COXI and eNOS were significantly higher in the myocardium of cyanotic than of acyanotic patients. PGC-1α transcript levels correlated with the levels of eNOS.
CONCLUSION: Mitochondrial biogenesis is activated in right ventricular outflow tract myocardium in congenital heart disease with cyanosis, which could be the adaptive response to chronic hypoxia and possibly involves eNOS up-regulation.
Authors:
Juan Xiao; Lin Chen; Xuefeng Wang; Mei Liu; Yingbin Xiao
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-08-02
Journal Detail:
Title:  Arquivos brasileiros de cardiologia     Volume:  99     ISSN:  1678-4170     ISO Abbreviation:  Arq. Bras. Cardiol.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-26     Completed Date:  2013-04-23     Revised Date:  2014-07-31    
Medline Journal Info:
Nlm Unique ID:  0421031     Medline TA:  Arq Bras Cardiol     Country:  Brazil    
Other Details:
Languages:  eng; por     Pagination:  780-8     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Child
Child, Preschool
Cyanosis / enzymology*,  physiopathology*
DNA Copy Number Variations
DNA, Mitochondrial / chemistry
Female
Gene Expression Regulation / physiology
Heart Defects, Congenital / enzymology*,  physiopathology
Humans
Male
Mitochondrial Size
Mitochondrial Turnover / physiology*
Myocardium / metabolism*
Nitric Oxide Synthase / metabolism
Nitric Oxide Synthase Type III / metabolism*
Reverse Transcriptase Polymerase Chain Reaction
Transcription Factors / metabolism
Young Adult
Chemical
Reg. No./Substance:
0/DNA, Mitochondrial; 0/Transcription Factors; 0/peroxisome-proliferator-activated receptor-gamma coactivator-1; EC 1.14.13.39/Nitric Oxide Synthase; EC 1.14.13.39/Nitric Oxide Synthase Type III

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