title: Diabetic hearts have lower basal urocortin levels that fail to increase after cardioplegic arrest: association with increased apoptosis and postsurgical cardiac dysfunction.
abstract: OBJECTIVE
  The present study investigated the cardioprotective role of urocortin (Ucn) and its relationship with protein kinase C (PKC)ε and PKCδ in patients with (DMPs) and without (NDMPs) diabetes mellitus after on-pump cardiac surgery (OPCS). The molecular mechanisms responsible for the reported worse outcomes of DMP after OPCS remain unknown.
  
  
  METHODS
  Two sequential biopsy specimens were obtained from the right atrium of 27 DMPs and 22 NDMPs before and after cardiopulmonary bypass.
  
  
  RESULTS
  Postcardioplegic induction of Ucn in NDMPs (P<.01) was not observed in the DMPs, whose precardioplegic Ucn levels were 50% lower than those in the NDMPs (P<.05). In the NDMPs, cardioplegic arrest increased PKCε mRNA and protein (P<.05); overexpression of PKCδ was not seen. In contrast, DMPs showed increased PKCδ expression (P<.01), with no change in PKCε. Apoptosis was more than twofold greater in the postcardioplegic samples from the DMPs than in those from the NDMPs. The apoptotic myocytes were Ucn negative and exhibited nuclear relocation of PKCδ. Enhanced PKCε/mitochondrial co-localization was observed in viable, Ucn-positive, myocytes. The leakage of troponin I documented in the DMPs was greater than that in the NDMPs, although the difference was not statistically significant (P=.06). Furthermore, despite a similar incidence of perioperative acute myocardial infarction, the DMPs did not show postoperative improvement of systolic or diastolic function, although that was seen in the NDMPs (P<.05).
  
  
  CONCLUSIONS
  Cardioplegic arrest failed to induce in DMPs myocyte overexpression of Ucn or PKCε but was associated with induction and mitochondrial relocation of PKCδ, resulting in apoptosis. Failure to overexpress Ucn in the DMPs was associated with apoptosis and cardiac dysfunction and, thus, might contribute to worse postoperative outcomes.
authors: Veterans Affairs Ann Arbor Health Care System, University of Michigan, Ann Arbor, Mich.
authors: Carol
authors: C
authors: Chen-Scarabelli
authors: Medical and Molecular Biology Unit, University College London, London, United Kingdom.
authors: Richard
authors: R
authors: Knight
authors: Medical and Molecular Biology Unit, University College London, London, United Kingdom.
authors: Anastasis
authors: A
authors: Stephanou
authors: Center for Heart and Vessel Preclinical Studies, St John Hospital and Medical Center, Wayne State University, Detroit, Mich.
authors: Gabriele
authors: G
authors: Scarabelli
authors: Division of Cardiothoracic Surgery, University of Verona, Verona, Italy.
authors: Francesco
authors: F
authors: Onorati
authors: Division of Cardiothoracic Surgery, University of Verona, Verona, Italy.
authors: Maddalena
authors: M
authors: Tessari
authors: Division of Cardiothoracic Surgery, University of Verona, Verona, Italy.
authors: Alessio
authors: A
authors: Rungatscher
authors: Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY.
authors: Jagat
authors: J
authors: Narula
authors: Center for Heart and Vessel Preclinical Studies, St John Hospital and Medical Center, Wayne State University, Detroit, Mich.
authors: Louis
authors: L
authors: Saravolatz
authors: Division of Cardiothoracic Surgery, University of Verona, Verona, Italy.
authors: Alessandro
authors: A
authors: Mazzucco
authors: Division of Cardiothoracic Surgery, University of Verona, Verona, Italy.
authors: Giuseppe
authors: G
authors: Faggian
authors: Center for Heart and Vessel Preclinical Studies, St John Hospital and Medical Center, Wayne State University, Detroit, Mich; Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: tiziano.scarabelli@stjohn.org.
authors: Tiziano M
authors: TM
authors: Scarabelli
mesh_terms: D000368:Aged; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D003324:Coronary Artery Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006324:Heart Arrest, Induced / Q000009:adverse effects*; D006325:Heart Atria / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008929:Mitochondria, Heart / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D051745:Protein Kinase C-delta / Q000235:genetics / Q000378:metabolism; D051744:Protein Kinase C-epsilon / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D019210:Troponin I / Q000097:blood; D054832:Urocortins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D019210:Troponin I; D054832:Urocortins; C497258:PRKCD protein, human; C497255:PRKCE protein, human; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon