title: Apoptosis and autophagy contribute to gender difference in cardiac ischemia-reperfusion induced injury in rats.
abstract: OBJECTIVE
  Gender difference in cardiac ischemia-reperfusion (IR) induced injury has been reported in animal models. However, a large-scale clinical trial found an increase in cardiovascular incidents in women with hormone replacement therapy. The present study is aimed to explore possible mechanisms of gender difference in cardiac IR induced injury.
  
  
  METHODS
  Male and female Sprague-Dawley rats were subjected to a 30-min coronary arterial occlusion followed by reperfusion. The infarct size and apoptotic cell number at 24h after reperfusion were significantly lower in female rats than in male rats.
  
  
  RESULTS
  Male rats expressed higher anti-apoptotic protein Bcl2 levels compared with female rats under physiological conditions. However, levels of Bcl2 were reduced significantly after IR in male rats but not in, female rats. Levels of pro-apoptotic protein, Bax and phospho-p38, showed similar under physiological conditions. In response to IR expression of Bax was markedly reduced in female rats but not in male rats, and expression of phospho-p38 was significantly increased in male rats but not in female rats. In addition, female rats showed marked increase of autophagy marker, ratio of LC3B to LC3A, while male rats significantly decreased the ratio in response to IR.
  
  
  CONCLUSIONS
  Gender difference in IR injury is due to the different regulation of anti-apoptotic protein, pro-apoptotic protein and autophagy protein levels in male rats and levels in female rats. Our results provide better understanding of sex differences in cardiac IR injury.
authors.affiliation: Department of Physiology, Medical College of Soochow University, 199 Ren-Ai Road, Dushu Lake Campus, Suzhou Industrial Park, Suzhou 215123, PR China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.forename: Li-Xun
authors.initials: LX
authors.lastname: Hu
authors.forename: Tao
authors.initials: T
authors.lastname: Dong
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Wang
authors.forename: Lin-Hui
authors.initials: LH
authors.lastname: Wang
authors.forename: Xi-Ping
authors.initials: XP
authors.lastname: Zhou
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Koji
authors.initials: K
authors.lastname: Murao
authors.forename: Shi-Qi
authors.initials: SQ
authors.lastname: Lu
authors.forename: Jing-Wei
authors.initials: JW
authors.lastname: Chen
authors.forename: Guo-Xing
authors.initials: GX
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001157:Arterial Occlusive Diseases / Q000473:pathology / Q000503:physiopathology; D001343:Autophagy / Q000502:physiology*; D015153:Blotting, Western; D003331:Coronary Vessels / Q000502:physiology; D005260:Female; D020287:In Situ Nick-End Labeling; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000473:pathology; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Apoptosis; Autophagy; Cardiac ischemia–reperfusion; Gender difference