title: Cardiac-specific PID1 overexpression enhances pressure overload-induced cardiac hypertrophy in mice.
abstract: OBJECTIVE
  PID1 was originally described as an insulin sensitivity relevance protein, which is also highly expressed in heart tissue. However, its function in the heart is still to be elucidated. Thus this study aimed to investigate the role of PID1 in the heart in response to hypertrophic stimuli.
  
  
  METHODS
  Samples of human failing hearts from the left ventricles of dilated cardiomyopathy (DCM) patients undergoing heart transplants were collected. Transgenic mice with cardiomyocyte-specific overexpression of PID1 were generated, and cardiac hypertrophy was induced by transverse aortic constriction (TAC). The extent of cardiac hypertrophy was evaluated by echocardiography as well as pathological and molecular analyses of heart samples.
  
  
  RESULTS
  A significant increase in PID1 expression was observed in failing human hearts and TAC-treated wild-type mouse hearts. When compared with TAC-treated wild-type mouse hearts, PID1-TG mouse showed a significant exacerbation of cardiac hypertrophy, fibrosis, and dysfunction. Further analysis of the signaling pathway in vivo suggested that these adverse effects of PID1 were associated with the inhibition of AKT, and activation of MAPK pathway.
  
  
  CONCLUSIONS
  Under pathological conditions, over-expression of PID1 promotes cardiac hypertrophy by regulating the Akt and MAPK pathway.
authors: Department of Cardiology, Nanjing Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University, Nanjing, China.
authors: Yaoqiu
authors: Y
authors: Liu
authors: Yahui
authors: Y
authors: Shen
authors: Jingai
authors: J
authors: Zhu
authors: Ming
authors: M
authors: Liu
authors: Xing
authors: X
authors: Li
authors: Yumei
authors: Y
authors: Chen
authors: Xiangqing
authors: X
authors: Kong
authors: Guixian
authors: G
authors: Song
authors: Lingmei
authors: L
authors: Qian
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000473:pathology; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018995:Myosin Heavy Chains / Q000235:genetics; D011312:Pressure; D011401:Promoter Regions, Genetic; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D014463:Ultrasonography; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; C514653:PID1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D018995:Myosin Heavy Chains