Pathological autophagy augments cell death in the diabetic heart

Background: Diabetic heart disease (DHD) is one of the major causes of mortality and morbidity in people with diabetes. DHD is characterised by the excessive loss of cardiovascular cells including cardiac stem cells. However, the exact mechanism leading to this loss remains unknown. Autophagy is a cellular degradation pathway that plays an important role in cellular homeostasis which becomes pathological when the balance is lost. Our recent studies conducted using mouse model of type-2 diabetes showed pathological autophagy in the diabetic heart. Current study aimed to understand if similar mechanism exists in the human diabetic heart. Methods: We collected right atrial appendage samples from 11 patients with type-2 diabetes (54-83 years of age), who underwent on-pump coronary artery bypass graft surgery at Dunedin Hospital. Samples from age-matched non-diabetic individuals served as the control. Total proteins were extracted and quantitative western blot analysis was carried out to study the expression pattern of the autophagy inducer beclin-1 and autophagy marker LC3-II proteins. Results: Clinical data showed no significant difference between diabetic and non-diabetic groups. However, quantitative western blot analysis of the right atrial appendage showed significant (p < 0.05, n = 11) increase in the autophagy markers, beclin-1 (1.26 0.6) and LC3-P (1.18 0.2) in the diabetic heart as compared to the non-diabetic heart. Conclusion: For the first time we demonstrate the existence of pathological autophagy in the human diabetic heart. These observations, therefore, invite a larger study to investigate the correlation between autophagy and functional alterations in the diabetic heart.