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Title: The mechanism of cell death in the human diabetic myocardium
Author: Chowdhry, T. Mohammed Fiyaz
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2006
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The importance of apoptosis in ischaemia-reoxygenation of the diabetic human heart is unclear. Right atrial appendages were obtained from non-diabetics, non-insulin dependent diabetics (NIDDM) and insulin dependent diabetics (IDDM) at the time of cardiac surgery. Free-hand tissue secretions were subjected to the following protocols: fresh tissue, aerobic control for 210 min, 90 min simulated ischaemia followed by 120 min reoxygenation (SI/R). Cell death by apoptosis and necrosis in non-ischaemic fresh tissue was greater in the NIDDM and the IDDM groups than in the non-diabetic group (p<0.05 in all instances). After SI/R, apoptosis and necrosis were also significantly greater in NIDDM and IDDM groups than in non-diabetics (p<0.05). The mean values of activation of Effector caspase were greater in fresh tissue in the NIDDM and IDDM groups than in the non-diabetic group (p<0.05) and values were further increased after SI/R in the NIDDM and IDDM groups as compared with non-diabetic group (p<0.05). Importantly caspase-3 inhibition reduced apoptosis by 94.0+/-1.6% in the myocardium from non-diabetics and 50.6+/-4.2% in the muscles from diabetics (p<0.05) without influencing necrosis. However, caspase -2 inhibition had no effect on either apoptosis or necrosis. Poly (ADP-ribose) Polymerase (PARP) inhibition resulted in a similar reduction in apoptosis (85.3+/-0.9% and 87.1+/-2.1%) and in necrosis (39.8+/-5.0% and 30.0+/-3.3%) in the muscles from non-diabetic and diabetics. The human diabetic myocardium is also more susceptible to ischaemia/reoxygenation injury than the non-diabetic myocardium, an effect that is mediated, at least in part, by caspase and PARP activation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available