Abstract 9636: Autophagy Plays a Critical Role in Maintenance of Cardiac Function in Diabetes
Although diabetic cardiomyopathy, which develops in the absence of major coronary artery disease, is one of the leading causes of heart failure, the pathogenesis is still unclear. Little is known on the relationship between diabetic cardiomyopathy and autophagy which is intracellular self digesting mechanism and reported in various pathologic conditions. Here, we investigated the perturbation of autophagy in diabetic hearts. We used GFP (green fluorescent protein)-LC3 (microtubule-associated protein 1 light chain 3) transgenic mice to monitor the autophagic vacuole in which type I diabetes was induced by an intraperitoneal injection of streptozotocin (250 mg/kg). Thirty-four diabetes mice were treated with saline or an autophagy inhibitor chloroquine (10mg/kg/day) (n=17 each) for 2 weeks while so were nondiabetes control group (n=17 each). Cardiac function was evaluated by echocardiography and cardiac catheterization. In diabetes mice, although systolic cardiac function and left ventricular diameter were similar to nondiabetes mice, diastolic cardiac function was aggravated compared with nondiabetes mice. And autophagic findings were significantly augmented in diabetes heart where expression levels of LC3-II, LC3-II/I ratio, p62, and cathepsin D were increased and abundant autophagic vacuoles and lysosome were observed under electron microscopy. The AMP-activated protein kinase (AMPK) was upregulated and myocardial ATP content was decreased in diabetes heart. Treatment with chloroquine provided no significant influence on the cardiac function and geometry in nondiabetes mice. In diabetes mice, however, chloroquine treatment caused significant left ventricular dilatation and aggravation of cardiac function (both systolic and diastolic), in which autohagic findings were significantly suppressed. In addition, chloroquine treatment brought about further reduction of ATP content and further activation of AMPK in the diabetes heart. In conclusion, our findings suggest a critical role of autophagy that compensates for lack of energy to maintain cardiac function in diabetes heart.
- © 2013 by American Heart Association, Inc.