title: Diabetes Upregulation of Cyclooxygenase 2 Contributes to Altered Coronary Reactivity After Cardiac Surgery.
abstract: BACKGROUND
  We hypothesized that upregulation of inducible cyclooxygenase 2 (COX-2) contributes to altered coronary arteriolar reactivity early after cardioplegic arrest and cardiopulmonary bypass (CP/CPB) in patients with diabetes mellitus who are undergoing cardiac surgery.
  
  
  METHODS
  The right atrial tissue samples of nondiabetes (ND), controlled diabetes (CDM), and uncontrolled diabetes (UDM) patients undergoing cardiac surgery were harvested before and after CP/CPB. Coronary arterioles (80 to 150 μm) were dissected from the harvested atrial tissue samples, cannulated, and pressurized. The changes in diameter were measured with video microscopy. The protein expression and localization of COX-1 and COX-2 were assayed by Western blot and immunohistochemistry.
  
  
  RESULTS
  In the diabetes arterioles, bradykinin-induced relaxation response was inhibited by the selective COX-2 inhibitor NS398 at baseline (p < 0.05). This effect was more pronounced in UDM arterioles than CDM (p < 0.05). After CP/CPB, bradykinin-induced responses in all groups were inhibited by NS398, but this effect was more pronounced in the UDM patients (p < 0.05). The intensities of COX-2 staining of coronary arterioles and COX-2 protein levels in myocardium were higher in diabetes than nondiabetes at baseline (p < 0.05). The post-CP/CPB protein levels of the inducible COX-2 were significantly increased compared with pre-CP/CPB values in all groups (p < 0.05), whereas this increase was higher with diabetes than with ND (p < 0.05). Furthermore, these effects were more profound in UDM than CDM (p < 0.05).
  
  
  CONCLUSIONS
  Diabetes and CP/CPB are associated with upregulation in COX-2 expression in human coronary vasculature. Upregulation of COX-2 expression may contribute to bradykinin-induced coronary arteriolar relaxation in diabetic patients undergoing cardiac surgery.
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island.
authors.forename: Jun
authors.initials: J
authors.lastname: Feng
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island.
authors.forename: Kelsey
authors.initials: K
authors.lastname: Anderson
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Singh
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island.
authors.forename: Afshin
authors.initials: A
authors.lastname: Ehsan
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island.
authors.forename: Hunter
authors.initials: H
authors.lastname: Mitchell
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island. Electronic address: fsellke@lifesapn.org.
authors.forename: Frank W
authors.initials: FW
authors.lastname: Sellke
mesh_terms: D000368:Aged; D015153:Blotting, Western; D006348:Cardiac Surgical Procedures; D003324:Coronary Artery Disease / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D003331:Coronary Vessels / Q000378:metabolism / Q000503:physiopathology*; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D003920:Diabetes Mellitus / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008833:Microcirculation / Q000502:physiology; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism; D015854:Up-Regulation; D014664:Vasodilation / Q000502:physiology*
chemical_list: D051546:Cyclooxygenase 2