Abstract 18096: Trehalose, a Natural Dissacharide, Reduces Cardiac Remodeling After Myocardial Infarction Through Autophagy Activation
Trehalose is a disaccharide synthesized by lower organisms. Trehalose has a high water retention capability in cells, thereby protecting intracellular organelles from disruption by the hydration/dehydration cycle during stress. Trehalose has been shown to exert extraordinary beneficial effects in mouse models of neurodegenerative disorders, by promoting the clearance of misfolded proteins through stimulation of autophagy. We investigated whether the administration of trehalose is beneficial during chronic myocardial infarction (MI), where the enhancement of misfolded protein clearance by autophagy should be protective. C57BL/6 mice were subjected to permanent left coronary artery ligation (LAD). After ligation, mice were divided into two groups of treatment: one group (TRE, N=9) was treated with trehalose (1 mg/g/day i.p for 48 h, and then 2% in the drinking water), while the other group (PLB, N=9) received placebo (regular water). After 4 weeks, the mortality tended to be lower in TRE than in PLB (11.1 vs. 33.3%, p=NS). TRE displayed a significant attenuation of LV dilation (LVEDD: 3.2 ± 0.1 vs. 3.9 ± 0.3 mm, p<0.05) and LV systolic dysfunction with respect to PLB (FS: 39.2 ± 2.0 vs. 28.8 ± 5.1%, p<0.05). Heart weight/tibia length (HW/TL, 7.4 ± 0.3 vs. 10.7 ± 1.4 mg/mm, p<0.05) and LV weight/tibia length (LVW/TL, 4.8 ± 0.2 vs. 6.8 ± 1.0 mg/mm, p<0.05) were also lower in TRE than PLB. These results demonstrate that trehalose reduces LV remodeling and heart failure after MI. We observed that trehalose administration markedly increased cardiac autophagy (LC3 puncta number, 4.1 ± 0.2 fold, p<0.05; p62 accumulation, 0.7 fold, p<0.05). Notably, when trehalose was administered to beclin-1 +/- mice, which present a defect in autophagy, the protective effects of trehalose on fractional shortening (TRE vs.PLB: 33.8 ± 3.8 vs. 24.7 ± 2.7%, p=NS) and LVW/TL (TRE vs.PLB: 6.0 ± 0.2 vs. 7.0 ± 0.8 mg/mm, p=NS) were attenuated, indicating that trehalose partially exerts its protective effects on cardiac remodeling through autophagy activation. In conclusion, trehalose prevents cardiac remodeling and LV dysfunction after MI. Trehalose activates autophagy, which plays a critical role in mediating the beneficial effect of trehalose during cardiac remodeling.
- © 2012 by American Heart Association, Inc.