The role of autophagy in doxorubicin-induced cardiotoxicity

Dirks‐Naylor, Amie J.

doi:10.1016/j.lfs.2013.10.013

Cited by 97 publications

(71 citation statements)

References 19 publications

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“…Cancer chemotherapy, particularly with anthracyclines, has long been associated with significant cardiotoxicity (93). The majority of human studies suggest that doxorubicin increases autophagy and likely contributes to cellular dysfunction and apoptosis (94). Notably, many preclinical studies are based on models of high-dose doxorubicin As discussed earlier, although excessive cardiomyocyte autophagy can be maladaptive, complete abrogation of autophagy is similarly maladaptive and can accelerate the progression to HF.…”

Section: Autophagy In Cardiovascular Diseasementioning

confidence: 99%

“…In some instances, autophagic flux was never evaluated. Doxorubicin may stimulate autophagy in the heart via depletion of GATA binding protein 4 and activation of ribosomal protein S6 kinase 1 (S6K1), which in turn may regulate essential autophagy genes (94). Rat models of doxorubicin-induced cardiomyopathy further implicate cardiomyocyte autophagy in the progression to HF (95).…”

Section: Autophagy In Other Cardiomyopathiesmentioning

confidence: 99%

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Autophagy in cardiovascular biology

Lavandero

Chiong

Rothermel³

et al. 2015

J. Clin. Invest.

280

211

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Autophagy in the vascular systemEndothelial cells. Autophagy can be regulated in vascular endothelial cells by compounds circulating in the bloodstream or localized within the subendothelial layer of atherosclerotic plaque. For example, in cultured HUVECs, vitamin D increases beclin 1, a key comCardiovascular disease is the leading cause of death worldwide. As such, there is great interest in identifying novel mechanisms that govern the cardiovascular response to disease-related stress. First described in failing hearts, autophagy within the cardiovascular system has been widely characterized in cardiomyocytes, cardiac fibroblasts, endothelial cells, vascular smooth muscle cells, and macrophages. In all cases, a window of optimal autophagic activity appears to be critical to the maintenance of cardiovascular homeostasis and function; excessive or insufficient levels of autophagic flux can each contribute to heart disease pathogenesis. In this Review, we discuss the potential for targeting autophagy therapeutically and our vision for where this exciting biology may lead in the future.

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Section: Autophagy In Cardiovascular Diseasementioning

confidence: 99%

Section: Autophagy In Other Cardiomyopathiesmentioning

confidence: 99%

Autophagy in cardiovascular biology

Lavandero

Chiong

Rothermel³

et al. 2015

J. Clin. Invest.

280

211

View full text Add to dashboard Cite

show abstract

“…However, its clinical use is limited by potential cardiotoxicity. We and others have recently shown that autophagic flux is impaired in the mouse models of doxorubicin-induced cardiotoxicity, which contributes to heart injury [14][15][16]. Moreover, we have shown that IF is capable of restoring autophagic flux and ameliorating pathological alterations including increased cytoplasmic vacuolization, fibrosis, apoptosis and generation of reactive oxygen species in both acute and chronic doxorubicin cardiotoxicity [16].…”

Section: If and Doxorubicin-induced Cardiotoxicitymentioning

confidence: 78%

Cardioprotective Effects of Intermittent Fasting

Zhu¹

2017

J Clin Diagn Res

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Calorie restriction, a dietary regimen reducing energy intake without causing malnutrition, prolongs lifespan and exerts medical and health benefits such as lowering metabolic risk factors for chronic diseases and ameliorating chronic conditions. Intermittent fasting (IF), a type of calorie restriction regimen, has attracted particular attention as it is cost-effective and more accessible while exerting the same or even enhanced beneficial effects on health and disease in laboratory animals and humans. In this review, we focus on the protective effects of IF on several types of heart diseases including myocardial ischemic injury, age-related cardiac hypertrophy, doxorubicin-induced cardiotoxicity and coronary heart disease risk factors. The findings summarized here implicate IF as a nonpharmacological, non-genetic preventive or therapeutic intervention for certain types of heart disease.

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“…Kawaguchi et al [29] concluded that the protection against Dox-induced injury extended by 48-h of fasting prior to treatment was due to restoration of autophagy. Autophagy is a conserved process among eukaryotic cells that sequesters cellular material via formation of a multimembrane-bound vacuole, an autophagosome, followed by degradation of the material via fusion of the autophagosome with a lysosome [43] . Autophagy can enhance cellular function and survival by degrading damaged or unwanted proteins and organelles such as mitochondria, as well as by modulating apoptosis [44] .…”

Section: Mechanism Of Fasting-induced Cardioprotection Against Dox Tomentioning

confidence: 99%

“…Furthermore, no other processes known to be affected by fasting were assessed in the study. Moreover, several studies have shown that stimulation of autophagy contributes to Dox-induced cardiotoxicity and protection is provided via inhibition of autophagy [43] . Thus the role of autophagy in Dox-induced cardiotoxicity, whether protective or pathological, is still under question.…”

Section: Mechanism Of Fasting-induced Cardioprotection Against Dox Tomentioning

confidence: 99%

Can short-term fasting protect against doxorubicin-induced cardiotoxicity?

Dirks‐Naylor

Kouzi

Yang

et al. 2014

WJBC

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a potential strategy to prevent Dox-induced cardiotoxicity. Future research should aim to determine the optimal regimen of fasting, confirmation that this regimen does not interfere with the antitumor properties of Dox, as well as the underlying mechanisms exerting the cardioprotective effects.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Fasting; Doxorubicin; Cardiotoxicity; Cardioprotection Core tip: Doxorubicin (Dox)-induced cardiotoxicity remains a significant cause of morbidity and mortality in cancer survivors, despite the intensive investigation of potential protective strategies. Studies have shown that shortterm fasting induces cardioprotective effects against Doxinduced injury. Importantly, evidence suggests that fasting may enhance the antitumor effects of Dox. Thus, shortterm fasting may be a feasible practice that can easily be incorporated into the treatment plans of cancer patients. Abstract Doxorubicin (Dox) is one of the most effective chemotherapeutic agents used in the treatment of several types of cancer. However the use is limited by cardiotoxicity. Despite extensive investigation into the mechanisms of toxicity and preventative strategies, Dox-induced cardiotoxicity still remains a major cause of morbidity and mortality in cancer survivors. Thus, continued research into preventative strategies is vital. Short-term fasting has proven to be cardioprotective against a variety of insults. Despite the potential, only a few studies have been conducted investigating its ability to prevent Dox-induced cardiotoxicity. However, all show proof-of-principle that short-term fasting is cardioprotective against Dox. Fasting affects a plethora of cellular processes making it difficult to discern the mechanism(s) translating fasting to cardioprotection, but may involve suppression of insulin and insulin-like growth factor-1 signaling with stimulated autophagy. It is likely that additional mechanisms also contribute. Importantly, the literature suggests that fasting may enhance the antitumor activity of Dox. Thus, fasting is a regimen that warrants further investigation as

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The role of autophagy in doxorubicin-induced cardiotoxicity

Cited by 97 publications

References 19 publications

Autophagy in cardiovascular biology

Autophagy in cardiovascular biology

Cardioprotective Effects of Intermittent Fasting

Can short-term fasting protect against doxorubicin-induced cardiotoxicity?

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