title: eNOS correlates with mitochondrial biogenesis in hearts of congenital heart disease with cyanosis.
abstract: 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 Î³ 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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Cardiovascular Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, PR, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Xiao
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Wang
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.forename: Yingbin
authors.initials: Y
authors.lastname: Xiao
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003490:Cyanosis / Q000201:enzymology* / Q000503:physiopathology*; D056915:DNA Copy Number Variations; D004272:DNA, Mitochondrial / Q000737:chemistry; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006330:Heart Defects, Congenital / Q000201:enzymology* / Q000503:physiopathology; D006801:Humans; D008297:Male; D053142:Mitochondrial Size; D063269:Mitochondrial Turnover / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; D014157:Transcription Factors; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III