title: The coexistence of nocturnal sustained hypoxia and obesity additively increases cardiac apoptosis.
abstract: BACKGROUND
  nocturnal sustained hypoxia during sleeping time has been reported in severe obesity, but no information regarding the cardiac molecular mechanism in the coexistence of nocturnal sustained hypoxia and obesity is available. This study evaluates whether the coexistence of nocturnal sustained hypoxia and obesity will increase cardiac Fas death receptor and mitochondrial-dependent apoptotic pathway.
  
  
  METHODS
  32 lean and 32 obese 5- to 6-mo-old rats with or without nocturnal sustained hypoxia were studied and assigned to one of four subgroups: normoxia lean (NL), normoxia obese (NO), hypoxia lean (HL, 12% O(2) for 8 h and 21% O(2) 16 h/day, 1 wk), and hypoxia obese (HO). The heart weight index, tail cuff plethysmography, echocardiography, hematoxylin-eosin staining, TUNEL assays, Western blotting, and RT-PCR were performed.
  
  
  RESULTS
  systolic and diastolic blood pressures in HO were higher than those in NL, and fractional shortening in HO was reduced compared with others. The whole heart weight, the left ventricular weight, the abnormal myocardial architecture, and TUNEL-positive apoptotic cells, as well as the activity of cardiac Fas-dependent and mitochondrial-dependent apoptotic pathway, were significantly increased in obese group or nocturnal sustained hypoxia group and were further increased when obesity and nocturnal sustained hypoxia coexisted, the evidence for which is based on decreases in an anti-apoptotic protein Bcl2 level and Bid and increases in Fas, FADD, pro-apoptotic Bad, BNIP3, cytosolic cytochrome c, activated caspase-8, activated caspase-9, and activated caspase-3.
  
  
  CONCLUSIONS
  The cardiac Fas receptor- and mitochondrial-dependent apoptotic pathways were more activated in obesity with coexistent nocturnal sustained hypoxia, which may represent one possible apoptotic mechanism for the development of heart failure in obesity with nocturnal sustained hypoxia.
authors.affiliation: Graduate Institute of Chinese Medical Science and Institute of Medical Science, China Medical Univ., No. 91, Hsueh-Shih Road, Taichung, 404, Taiwan.
authors.forename: Shin-Da
authors.initials: SD
authors.lastname: Lee
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Kuo
authors.forename: Da-Tian
authors.initials: DT
authors.lastname: Bau
authors.forename: Fu-Yang
authors.initials: FY
authors.lastname: Ko
authors.forename: Fong-Li
authors.initials: FL
authors.lastname: Wu
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Kuo
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.forename: Paulus S
authors.initials: PS
authors.lastname: Wang
authors.forename: Min-Chi
authors.initials: MC
authors.lastname: Lu
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001794:Blood Pressure / Q000502:physiology; D015153:Blotting, Western; D001835:Body Weight / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D045304:Cytochromes c / Q000096:biosynthesis / Q000235:genetics; D003600:Cytosol / Q000378:metabolism; D004452:Echocardiography; D004591:Electrophoresis, Polyacrylamide Gel; D000860:Hypoxia / Q000150:complications / Q000473:pathology*; D020287:In Situ Nick-End Labeling; D008565:Membrane Proteins / Q000096:biosynthesis; D008929:Mitochondria, Heart / Q000502:physiology; D024101:Mitochondrial Proteins; D009206:Myocardium / Q000473:pathology*; D009765:Obesity / Q000150:complications / Q000473:pathology*; D009929:Organ Size / Q000502:physiology; D010991:Plethysmography; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011924:Rats, Zucker; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020181:Sleep Apnea, Obstructive / Q000150:complications / Q000473:pathology*; D016277:Ventricular Function, Left / Q000502:physiology; D019014:fas Receptor / Q000378:metabolism
chemical_list: C505650:BNIP3 protein, rat; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011518:Proto-Oncogene Proteins; D019014:fas Receptor; D012313:RNA; D045304:Cytochromes c; D020169:Caspases