title: Involvement of exogenous H2S in recovery of cardioprotection from ischemic post-conditioning via increase of autophagy in the aged hearts.
abstract: BACKGROUND
  Hydrogen sulfide (H2S), which is a member of the gasotransmitter family, plays an important physiological and pathological role in cardiovascular system. Ischemic post-conditioning (PC) provides myocardial protective effect in the young hearts but not in the aged hearts. Exogenous H2S restores PC-induced cardioprotection by inhibition of mitochondrial permeability transition pore (mPTP) in the aged hearts. However, whether H2S contributes to the recovery of PC-induced cardioprotection via up-regulation of autophagy in the aged hearts is unclear.
  
  
  METHODS
  The isolated aged rat hearts (24-months-old, 450-500g) and aged cardiomyocytes-induced by d-galactose were exposed to an ischemia/reperfusion (I/R) and PC protocol.
  
  
  RESULTS
  We found PC lost cardioprotection in the aged hearts and cardiomyocytes. NaHS (a H2S donor) significantly restored cardioprotection of PC through decreasing myocardial damage, infarct size, and apoptosis, improving cardiac function, increasing cell viability and autophagy in the aged hearts and cardiomyocytes. 3-MA (an autophagy inhibitor) abolished beneficial effect of NaHS in the aged hearts. In addition, in the aged cardiomyocytes, NaHS up-regulated AMPK/mTOR pathway, and the effect of NaHS on PC was similar to the overexpression of Atg 5, treatment of AICAR (an AMPK activator) or Rapamycin (a mTOR inhibitor, an autophagy activator), respectively.
  
  
  CONCLUSIONS
  These results suggest that exogenous H2S restores cardioprotection from PC by up-regulation of autophagy via activation of AMPK/mTOR pathway in the aged hearts and cardiomyocytes.
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China; The Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China.
authors.forename: Junting
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Osteology, The First Hospital of Harbin, Harbin, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China; The Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China.
authors.forename: Weiming
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China; The Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China; The Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China.
authors.forename: Yuehong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China; The Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China.
authors.forename: Shuzhi
authors.initials: S
authors.lastname: Bai
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China; The Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China.
authors.forename: Xiaoxue
authors.initials: X
authors.lastname: Li
authors.affiliation: The Cardiovascular and Metabolic Research Unit, Laurentian University, Sudbury, Canada.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: The Cardiovascular and Metabolic Research Unit, Laurentian University, Sudbury, Canada.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China; The Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China. Electronic address: hongzhuli61@163.com.
authors.forename: Hongzhu
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, China; The Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China. Electronic address: xucq45@126.com.
authors.forename: Changqing
authors.initials: C
authors.lastname: Xu
mesh_terms: D000375:Aging / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D000818:Animals; D001343:Autophagy / Q000187:drug effects / Q000502:physiology*; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D006862:Hydrogen Sulfide / Q000494:pharmacology / Q000627:therapeutic use*; D057775:Ischemic Postconditioning / Q000379:methods*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009924:Organ Culture Techniques; D011897:Random Allocation; D051381:Rats; D020127:Recovery of Function / Q000187:drug effects / Q000502:physiology*
chemical_list: D002316:Cardiotonic Agents; D006862:Hydrogen Sulfide
keywords: Aged cardiomyocytes; Aged heart; Autophagy; Hydrogen sulfide; Post-conditioning