title: High basal level of autophagy in high-altitude residents attenuates myocardial ischemia-reperfusion injury.
abstract: OBJECTIVE
  Hypoxia can induce autophagy, which plays an important role in cardioprotection. The present study tested the hypothesis that patients with congenital heart disease living at a high altitude could resist ischemia-reperfusion injury better than those at a low altitude, through elevated basal autophagy by chronic hypoxia.
  
  
  METHODS
  Twelve Tibetan patients residing at a high altitude of >3000 m and 12 Han patients residing at a low altitude of <500 m with simple atrial or ventricular septal defects were prospectively recruited. All patients underwent cardiopulmonary bypass, maintaining a flow rate of approximately 2.4 to 2.8 L/min/m2 and mean arterial pressure of ≥40 to 60 mm Hg. Myocardial ischemia-reperfusion injury between the 2 groups was compared using cardiac troponin I, brain natriuretic peptide, hematoxylin eosin staining, and the terminal deoxynucleotidyl transferase dUTP nick end labeling test. Autophagy-related proteins microtubule-associated protein 1 light chain 3 II (LC3II), Beclin1, and lysosomal-associated membrane protein 2 (LAMP2) and their upstream protein BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 (Bnip3) were evaluated with Western blotting.
  
  
  RESULTS
  The maximal cardiac troponin I concentration and increasing x-fold of brain natriuretic peptide in the high-altitude group were obviously lower than those in the low-altitude group (3.10±0.77 vs 7.10±2.28 ng/mL and 2.51±0.94 vs 14.66±6.83, respectively). The preoperative and postoperative levels of LC3II, LAMP2, and upstream Bnip3 in the high-altitude group were obviously greater. No difference was found in the Beclin1 level between the 2 groups at baseline or ischemia-reperfusion.
  
  
  CONCLUSIONS
  Patients living at a high altitude with congenital heart disease resisted ischemia-reperfusion injury during cardiac surgery better than those at a low altitude, possibly through elevated basal autophagy induced by chronic hypoxia.
authors.affiliation: Department of Cardiovascular Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yijie
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Cardiovascular Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Cardiovascular Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Cardiovascular Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Cardiovascular Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Shen
authors.affiliation: Department of Cardiovascular Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Cardiovascular Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China. Electronic address: zhongqianjin@qq.com.
authors.forename: Qianjin
authors.initials: Q
authors.lastname: Zhong
mesh_terms: D000293:Adolescent; D000531:Altitude; D051017:Apoptosis Regulatory Proteins / Q000097:blood; D001343:Autophagy / Q000502:physiology*; D000071186:Beclin-1; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D002315:Cardiopulmonary Bypass; D002648:Child; D005260:Female; D006330:Heart Defects, Congenital / Q000097:blood / Q000503:physiopathology* / Q000601:surgery*; D006801:Humans; D000860:Hypoxia / Q000097:blood / Q000503:physiopathology; D020287:In Situ Nick-End Labeling; D052119:Lysosomal-Associated Membrane Protein 2 / Q000097:blood; D008297:Male; D008565:Membrane Proteins / Q000097:blood; D008869:Microtubule-Associated Proteins / Q000097:blood; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000517:prevention & control*; D020097:Natriuretic Peptide, Brain / Q000097:blood; D011446:Prospective Studies; D018609:Tibet; D019210:Troponin I / Q000097:blood
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D015415:Biomarkers; C497811:LAMP2 protein, human; D052119:Lysosomal-Associated Membrane Protein 2; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D019210:Troponin I; D020097:Natriuretic Peptide, Brain