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Citations to this article

Enhanced autophagy ameliorates cardiac proteinopathy
Md. Shenuarin Bhuiyan, … , Junichi Sadoshima, Jeffrey Robbins
Md. Shenuarin Bhuiyan, … , Junichi Sadoshima, Jeffrey Robbins
Published November 1, 2013
Citation Information: J Clin Invest. 2013;123(12):5284-5297. https://doi.org/10.1172/JCI70877.
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Research Article Cardiology Article has an altmetric score of 7

Enhanced autophagy ameliorates cardiac proteinopathy

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Abstract

Basal autophagy is a crucial mechanism in cellular homeostasis, underlying both normal cellular recycling and the clearance of damaged or misfolded proteins, organelles and aggregates. We showed here that enhanced levels of autophagy induced by either autophagic gene overexpression or voluntary exercise ameliorated desmin-related cardiomyopathy (DRC). To increase levels of basal autophagy, we generated an inducible Tg mouse expressing autophagy-related 7 (Atg7), a critical and rate-limiting autophagy protein. Hearts from these mice had enhanced autophagy, but normal morphology and function. We crossed these mice with CryABR120G mice, a model of DRC in which autophagy is significantly attenuated in the heart, to test the functional significance of autophagy activation in a proteotoxic model of heart failure. Sustained Atg7-induced autophagy in the CryABR120G hearts decreased interstitial fibrosis, ameliorated ventricular dysfunction, decreased cardiac hypertrophy, reduced intracellular aggregates and prolonged survival. To determine whether different methods of autophagy upregulation have additive or even synergistic benefits, we subjected the autophagy-deficient CryABR120G mice and the Atg7-crossed CryABR120G mice to voluntary exercise, which also upregulates autophagy. The entire exercised Atg7-crossed CryABR120G cohort survived to 7 months. These findings suggest that activating autophagy may be a viable therapeutic strategy for improving cardiac performance under proteotoxic conditions.

Authors

Md. Shenuarin Bhuiyan, J. Scott Pattison, Hanna Osinska, Jeanne James, James Gulick, Patrick M. McLendon, Joseph A. Hill, Junichi Sadoshima, Jeffrey Robbins

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2014 2009 Total
Citations: 6 14 6 16 13 26 11 19 20 19 18 13 1 182
Citation information
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Citations to this article in year 2017 (20)

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Nature Reviews Drug Discovery 2017
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Myocardial stress and autophagy: mechanisms and potential therapies
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Nature Reviews Cardiology 2017
Sigmar1 regulates endoplasmic reticulum stress-induced C/EBP-homologous protein expression in cardiomyocytes
S Alam, CS Abdullah, R Aishwarya, AW Orr, J Traylor, S Miriyala, M Panchatcharam, CB Pattillo, MS Bhuiyan
Bioscience Reports 2017
New and revisited approaches to preserving the reperfused myocardium
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PloS one 2017
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J Li, W Ma, G Yue, Y Tang, I Kim, NL Weintraub, X Wang, H Su
Journal of Molecular and Cellular Cardiology 2017
An Unbiased High-Throughput Screen to Identify Novel Effectors That Impact on Cardiomyocyte Aggregate LevelsNovelty and Significance
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PloS one 2017
Potential signaling pathways of acute endurance exercise-induced cardiac autophagy and mitophagy and its possible role in cardioprotection
Y Lee, I Kwon, Y Jang, W Song, LM Cosio-Lima, MH Roltsch
The Journal of Physiological Sciences 2017
Voluntary running exercise protects against sepsis-induced early inflammatory and pro-coagulant responses in aged mice
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Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease 2017

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