| First Author | Zhu H | Year | 2007 |
| Journal | J Clin Invest | Volume | 117 |
| Issue | 7 | Pages | 1782-93 |
| PubMed ID | 17607355 | Mgi Jnum | J:124190 |
| Mgi Id | MGI:3721015 | Doi | 10.1172/JCI27523 |
| Citation | Zhu H, et al. (2007) Cardiac autophagy is a maladaptive response to hemodynamic stress. J Clin Invest 117(7):1782-93 |
| abstractText | Cardiac hypertrophy is a major predictor of heart failure and a prevalent disorder with high mortality. Little is known, however, regarding mechanisms governing the transition from stable cardiac hypertrophy to decompensated heart failure. Here, we tested the role of autophagy, a conserved pathway mediating bulk degradation of long-lived proteins and cellular organelles that can lead to cell death. To quantify autophagic activity, we engineered a line of 'autophagy reporter' mice and confirmed that cardiomyocyte autophagy can be induced by short-term nutrient deprivation in vivo. Pressure overload induced by aortic banding induced heart failure and greatly increased cardiac autophagy. Load-induced autophagic activity peaked at 48 hours and remained significantly elevated for at least 3 weeks. In addition, autophagic activity was not spatially homogeneous but rather was seen at particularly high levels in basal septum. Heterozygous disruption of the gene coding for Beclin 1, a protein required for early autophagosome formation, decreased cardiomyocyte autophagy and diminished pathological remodeling induced by severe pressure stress. Conversely, Beclin 1 overexpression heightened autophagic activity and accentuated pathological remodeling. Taken together, these findings implicate autophagy in the pathogenesis of load-induced heart failure and suggest it may be a target for novel therapeutic intervention. |
