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Published on: June 14, 2016
Intracellular protein aggregation is a proximal trigger of cardiomyocyte autophagy
Paul Tannous1, Hongxin Zhu, Andriy Nemchenko
1Department of Internal Medicine, University of Texas Southwestern Medical Center, 6000 Harry Hines Blvd, Dallas, TX 75390-8573, USA.
Circulation
|June 11, 2008
Summary
Protein aggregation triggers cardiomyocyte autophagy during heart stress. Autophagy helps clear these protein aggregates, preventing further damage in conditions like pressure-overload heart disease.
Area of Science:
- Cardiovascular Biology
- Cellular Stress Response
- Molecular Cardiology
Background:
- Cardiovascular stress, including pressure overload, ischemia, and infarction-reperfusion injury, increases autophagic activity in cardiomyocytes.
- The molecular mechanisms stimulating autophagy in stressed myocardium remain largely unknown.
- Autophagy degrades damaged proteins and organelles, a critical cellular housekeeping process.
Purpose of the Study:
- To investigate whether stress-induced protein aggregation acts as a trigger for cardiomyocyte autophagy.
- To explore the role of autophagy in managing protein aggregates in the stressed heart.
Main Methods:
- Examined left ventricular tissue from pressure-overloaded hearts for protein aggregates and aggresome-like structures.
- Utilized cultured cardiomyocytes to induce protein accumulation by inhibiting proteasome activity.
- Assessed the impact of autophagy attenuation on aggresome formation and size.
Main Results:
- Pressure overload led to the accumulation of ubiquitinated protein aggregates and aggresome-like structures in the heart.
- Protein aggregation induced by proteasome inhibition in cultured cardiomyocytes was sufficient to trigger autophagy.
- Reducing autophagic activity significantly increased aggresome size and abundance, indicating autophagy's role in clearance.
Conclusions:
- Protein aggregation serves as a proximal trigger for cardiomyocyte autophagy in response to hemodynamic stress.
- Autophagic activity plays a crucial role in mitigating the formation and accumulation of protein aggregates and aggresomes in the heart.
- These findings establish a link between hemodynamic stress, protein aggregation, and autophagy, classifying pressure-overload heart disease within proteinopathies.
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