title: Cardiopulmonary Bypass Decreases Activation of the Signal Transducer and Activator of Transcription 3 (STAT3) Pathway in Diabetic Human Myocardium.
abstract: BACKGROUND
  Cardiopulmonary bypass (CPB) is associated with increased myocardial oxidative stress and apoptosis in diabetic patients. A mechanistic understanding of this relationship could have therapeutic value. To establish a possible mechanism, we compared the activation of the cardioprotective signal transducer and activator of transcription 3 (STAT3) pathway between patients with uncontrolled diabetes (UD) and nondiabetic (ND) patients.
  
  
  METHODS
  Right atrial tissue and serum were collected before and after CPB from 80 patients, 39 ND and 41 UD (HbA1c ≥ 6.5), undergoing cardiac operations. The samples were evaluated with Western blotting, immunohistochemistry, and microarray.
  
  
  RESULTS
  On Western blot, leptin levels were significantly increased in ND post-CPB (p < 0.05). Compared with ND, the expression of Janus kinase 2 and phosphorylation (p-) of STAT3 was significantly decreased in UD (p < 0.05). The apoptotic proteins p-Bc12/Bc12 and caspase 3 were significantly increased (p < 0.05), antiapoptotic proteins Mcl-1, Bcl-2, and p-Akt were significantly decreased (p < 0.05) in UD compared with ND. The microarray data suggested significantly increased expression of interleukin-6 R, proapoptotic p-STAT1, caspase 9, and decreased expression of Bc12 and protein inhibitor of activated STAT1 antiapoptotic genes (p = 0.05) in the UD patients. The oxidative stress marker nuclear factor-κB was significantly higher (p < 0.05) in UD patients post-CPB compared with the pre-CPB value, but was decreased, albeit insignificantly, in ND patients post-CPB.
  
  
  CONCLUSIONS
  Compared with ND, UD myocardium demonstrated attenuation of the cardioprotective STAT3 pathway. Identification of this mechanism offers a possible target for therapeutic modulation.
authors.affiliation: Department of Anesthesiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Khurram
authors.initials: K
authors.lastname: Owais
authors.affiliation: Department of Anesthesiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Thomas
authors.initials: T
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Feroze
authors.initials: F
authors.lastname: Mahmood
authors.affiliation: Department of Anesthesiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Jeffery
authors.initials: J
authors.lastname: Hubbard
authors.affiliation: Department of Anesthesiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Rabya
authors.initials: R
authors.lastname: Saraf
authors.affiliation: Department of Anesthesiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Amit
authors.initials: A
authors.lastname: Bardia
authors.affiliation: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Kamal R
authors.initials: KR
authors.lastname: Khabbaz
authors.affiliation: Department of Anesthesiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Yunping
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Bioinformatics and Systems Biology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
authors.forename: Manoj
authors.initials: M
authors.lastname: Bhasin
authors.affiliation: Department of Bioinformatics and Systems Biology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Division of Cardiothoracic Surgery, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island.
authors.forename: Ashraf A
authors.initials: AA
authors.lastname: Sabe
authors.affiliation: Division of Cardiothoracic Surgery, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island.
authors.forename: Frank
authors.initials: F
authors.lastname: Sellke
authors.affiliation: Department of Anesthesiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. Electronic address: rmatya11@bidmc.harvard.edu.
authors.forename: Robina
authors.initials: R
authors.lastname: Matyal
mesh_terms: D000368:Aged; D017209:Apoptosis; D015153:Blotting, Western; D002315:Cardiopulmonary Bypass; D004247:DNA / Q000235:genetics*; D058065:Diabetic Cardiomyopathies / Q000235:genetics* / Q000378:metabolism / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D050796:STAT3 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D050796:STAT3 Transcription Factor; D004247:DNA