title: Inhibition of Uncoupling Protein 2 Attenuates Cardiac Hypertrophy Induced by Transverse Aortic Constriction in Mice.
abstract: BACKGROUND
  Uncoupling protein 2 (UCP2) is critical in regulating energy metabolism. Due to the significant change in energy metabolism of myocardium upon pressure overload, we hypothesize that UCP2 could contribute to the etiology of cardiac hypertrophy.
  
  
  METHODS
  Adult male C57BL/6J mice were subjected to pressure overload by using transverse aortic constriction (TAC), and then received genipin (a UCP2 selective inhibitor; 25 mg/kg/d, ip) or vehicle for three weeks prior to histologic assessment of myocardial hypertrophy. ATP concentration, ROS level, and myocardial apoptosis were also examined. A parallel set of experiments was also conducted in UCP2-/- mice.
  
  
  RESULTS
  TAC induced left ventricular hypertrophy, as reflected by increased ventricular weight/thickness and increased size of myocardial cell (vs. sham controls). ATP concentration was decreased; ROS level was increased. Apoptosis and fibrosis markers were increased. TAC increased mitochondrial UCP2 expression in the myocardium at both mRNA and protein levels. Genipin treatment attenuated cardiac hypertrophy and the histologic/biochemical changes described above. Hypertrophy and associated changes induced by TAC in UCP2-/- mice were much less pronounced than in WT mice.
  
  
  CONCLUSIONS
  Blocking UCP2 expression attenuates cardiac hypertrophy induced by pressure overload.
authors.affiliation: Center for Kidney Disease, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Xiao-Bing
authors.initials: XB
authors.lastname: Ji
authors.forename: Xiu-Rong
authors.initials: XR
authors.lastname: Li
authors.lastname: Hao-Ding
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Ping
authors.initials: P
authors.lastname: Wen
authors.forename: Chun-Sun
authors.initials: CS
authors.lastname: Dai
authors.forename: Jun-Wei
authors.initials: JW
authors.lastname: Yang
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000473:pathology*; D006332:Cardiomegaly / Q000209:etiology / Q000517:prevention & control*; D003251:Constriction, Pathologic; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000071246:Uncoupling Protein 2
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; C000604390:Ucp2 protein, mouse; D000071246:Uncoupling Protein 2; D000255:Adenosine Triphosphate