Abstract 16440: Altered Apoptosis-Related Signaling after Cardioplegic Arrest in Patients with Type 2 Uncontrolled Diabetes
Background: We investigated the effects of cardioplegic arrest and reperfusion (CP/Rep) on myocardial apoptosis and key apoptotic mediators, such as apoptosis-inducing factor (AIF), caspase-3, PARP and protein oxidation in the type 2-uncontrolled diabetic (UDM), and type 2-controlled diabetic (CDM), and non-diabetic (ND) patients.
Methods and Results: Right atrial tissue was harvested pre- and post-CP/Rep from the ND patients (HbA1C = 5.4 ± 0.12), the CDM patients (HbA1C = 6.5 ± 0.15 ) and UDM patients (HbA1C = 9.6 ± 0.25) undergoing coronary artery bypass grafting ( n = 8/group). TUNEL staining was used for identification of apoptotic cells. Total and/or modified AIF, caspase 3 and PARP were quantified by immunoblotting. There were no significant differences in the number of apoptotic cells and levels of total AIF protein expression in the pre-CP/Rep atrial tissue between ND and CDM groups. There were no changes of total/cleaved caspase 3 and total PARP expression between pre- and post-CP/Rep tissues in all three groups. In contrast, the number of apoptotic cells and levels of total AIF in the pre-CP/Rep atrial tissue from the UDM patients were significantly increased as compared with those of ND patients (P<0.05). The number of apoptotic cells, and levels of AIF (ND: P= 0.04; CDM: P = 0.02; UDM: P = 0.01) in post-CP/Rep atrial tissue were increased in all three groups as compared with those of pre-CP/Rep. These increases after CP/Rep were more pronounced in the UDM group (AIF : P = 0.009 vs. ND; P = 0.01 vs. CDM). Protein oxidation and nitrotyrosine in atrial tissue were significantly increased in the UDM group as compared with those of ND group or CDM. In contrast, there were no significant differences in the development of apoptosis, and protein expression of total AIF, caspase 3 and PARP, and protein oxidation in the post-CP/Rep atrial tissue between ND and CDM groups.
Conclusion: Uncontrolled diabetes is associated with increases in myocardial apoptosis and key apoptosis mediator AIF at the baseline and in the setting of CP/Rep, possibly due to the increased oxidative and nitrosative stress.
- © 2012 by American Heart Association, Inc.