Skip to main content
Article thumbnail
Location of Repository

Diabetes increases apoptosis and necrosis in the ischemic and non-ischemic human myocardium: role of caspases and poly (ADP-ribose) polymerase

By Mohammed F. Chowdhry, Hunaid A. Vohra and Manuel Galiñanes

Abstract

This is the authors' final draft of the paper published as Journal of Thoracic and Cardiovascular Surgery, 2007, 134(1), pp.127-131. The published version is available in Science Direct, via http://dx.doi.org/10.1016/j.jtcvs.2006.12.059Background: Diabetes is an important predictor of morbidity and mortality after cardiac surgery but the reason is unclear. Therefore the aims of these studies were to elucidate whether cell death is greater in the ischemic and non- ischemic diabetic human myocardium than in the non-diabetic and to investigate the underlying mechanism.\ud Methods: The right atrial appendages (n=8/group) of non-diabetics, non-insulin dependent diabetics (NIDDM) and insulin dependent diabetics (IDDM) were subjected to 90 minutes simulated ischemia/120 minutes reoxygenation (SI/R). Tissue injury was measured by the release of CK into the media, and cellular apoptosis and necrosis were assessed in tissue by the TUNEL assay and propidium iodide. Initiator and effector caspases activation was also measured.\ud Results: Apoptosis and necrosis were greater in the NIDDM and the IDDM groups than in the non-diabetic group both in fresh tissue and after SI/R. Activation of effector caspases was also higher in the NIDDM and IDDM groups than in the non-diabetic group after SI/R. Caspase-3 inhibition reduced apoptosis in all study groups without influencing necrosis; however, PARP inhibition resulted in a similar reduction in apoptosis and in necrosis in all groups and caspase-2 inhibition did not.\ud Conclusions: Diabetes increases both apoptosis and necrosis in the human myocardium in fresh and after being subjected to ischemia/reoxygenation, an effect that is mediated, at least in part, by caspase-3 and PARP activation. These results may explain the increased cardiac-related morbidity and mortality during cardiac surgery in patients with diabetes

Publisher: Elsevier
Year: 2007
DOI identifier: 10.1016/j.jtcvs.2006.12.059
OAI identifier: oai:lra.le.ac.uk:2381/862

Suggested articles


To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.