Objectives: The present study investigated the cardioprotective role of urocortin (Ucn) and its relationship with protein kinase C (PKC)epsilon and PKC delta 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 PKC epsilon mRNA and protein (P < .05); overexpression of PKC delta was not seen. In contrast, DMPs showed increased PKC delta expression (P < .01), with no change in PKC epsilon. 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 PKC delta. Enhanced PKC epsilon/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 PKC epsilon but was associated with induction and mitochondrial relocation of PKC delta, 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.
Diabetic hearts have lower basal urocortin levels that fail to increase after cardioplegic arrest: Association with increased apoptosis and postsurgical cardiac dysfunction
Francesco Onorati;RUNGATSCHER, Alessio;FAGGIAN, Giuseppe;
2014-01-01
Abstract
Objectives: The present study investigated the cardioprotective role of urocortin (Ucn) and its relationship with protein kinase C (PKC)epsilon and PKC delta 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 PKC epsilon mRNA and protein (P < .05); overexpression of PKC delta was not seen. In contrast, DMPs showed increased PKC delta expression (P < .01), with no change in PKC epsilon. 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 PKC delta. Enhanced PKC epsilon/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 PKC epsilon but was associated with induction and mitochondrial relocation of PKC delta, 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.
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