title: Effect of mitochondrial aldehyde dehydrogenase-2 genotype on cardioprotection in patients with congenital heart disease.
abstract: OBJECTIVE
  About 40% of East Asians carry an aldehyde dehydrogenase-2*2 (ALDH2*2) allele, and the influence of the ALDH2*2 allele on human cardioprotection has not been studied. This study was designed to evaluate the effect of ALDH2*2 allele on cardioprotection of patients with congenital heart diseases after open-heart surgery.
  
  
  RESULTS
  The right atrial appendage was harvested before performing cardiopulmonary bypass in cyanotic and acyanotic congenital heart disease groups (n = 20 per group). Tissues were assayed to determine the impact of cyanosis on metabolic remodelling. A prospective cohort of Tetralogy of Fallot (TOF) patients (n = 118) was recruited to investigate the influence of the ALDH2*2 allele on cardioprotection after surgical repair. Myocardium samples were dissected after cardioplegia. ALDH2 activity, oxidative stress and glutathione (GSH) levels, and activating transcription factor-4 (ATF4) were analysed. After genotyping and grouping, all of the experimental and clinical results were compared between ALDH2*2 carriers and non-carriers. Cyanosis inhibited ALDH2 activity and led to aldehyde accumulation in ALDH2*2 carriers. This accumulation in turn increased expression of ATF4 and resulted in larger myocardium GSH pools. The differences in ALDH2 activity and GSH level between carriers and non-carriers disappeared during cardioplegic arrest, and more aldehydes accumulated in the non-carriers. Consequently, ALDH2*2 carriers showed lower postoperative troponin I, inotrope score, and shorter postoperative length of ICU and hospital stay.
  
  
  CONCLUSIONS
  ALDH2*2 carriers with cyanotic congenital heart disease were associated with an induced metabolic remodelling phenotype and a compensatory myocardium GSH pool. When ALDH2 activity was impaired during open-heart surgery, this larger GSH pool could lead to unexpectedly better cardioprotection. This may aid in the prediction of cardioprotection outcomes and identification of individualized cardioprotective strategies.
authors.affiliation: State Key Laboratory of Cardiovascular Medicine, Fuwai Hospital, National Center for Cardiovascular Disease, Beijing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Ding-xu
authors.initials: DX
authors.lastname: Gong
authors.forename: Yu-jian
authors.initials: YJ
authors.lastname: Zhang
authors.forename: Shou-jun
authors.initials: SJ
authors.lastname: Li
authors.forename: Shengshou
authors.initials: S
authors.lastname: Hu
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D002315:Cardiopulmonary Bypass / Q000379:methods; D002316:Cardiotonic Agents; D003250:Constriction; D005260:Female; D005838:Genotype; D006330:Heart Defects, Congenital / Q000235:genetics* / Q000601:surgery; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D008929:Mitochondria, Heart / Q000201:enzymology / Q000235:genetics*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D011446:Prospective Studies
chemical_list: D002316:Cardiotonic Agents; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial