Early detection of doxorubicin-induced cardiotoxicity in rats by its cardiac metabolic signature assessed with hyperpolarized MRI View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2020-11-19

AUTHORS

Kerstin N. Timm, Charith Perera, Vicky Ball, John A. Henry, Jack J. Miller, Matthew Kerr, James A. West, Eshita Sharma, John Broxholme, Angela Logan, Dragana Savic, Michael S. Dodd, Julian L. Griffin, Michael P. Murphy, Lisa C. Heather, Damian J. Tyler

ABSTRACT

Doxorubicin (DOX) is a widely used chemotherapeutic agent that can cause serious cardiotoxic side effects culminating in congestive heart failure (HF). There are currently no clinical imaging techniques or biomarkers available to detect DOX-cardiotoxicity before functional decline. Mitochondrial dysfunction is thought to be a key factor driving functional decline, though real-time metabolic fluxes have never been assessed in DOX-cardiotoxicity. Hyperpolarized magnetic resonance imaging (MRI) can assess real-time metabolic fluxes in vivo. Here we show that cardiac functional decline in a clinically relevant rat-model of DOX-HF is preceded by a change in oxidative mitochondrial carbohydrate metabolism, measured by hyperpolarized MRI. The decreased metabolic fluxes were predominantly due to mitochondrial loss and additional mitochondrial dysfunction, and not, as widely assumed hitherto, to oxidative stress. Since hyperpolarized MRI has been successfully translated into clinical trials this opens up the potential to test cancer patients receiving DOX for early signs of cardiotoxicity. More... »

PAGES

692

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s42003-020-01440-z

DOI

http://dx.doi.org/10.1038/s42003-020-01440-z

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1132740319

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/33214680


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22 schema:description Doxorubicin (DOX) is a widely used chemotherapeutic agent that can cause serious cardiotoxic side effects culminating in congestive heart failure (HF). There are currently no clinical imaging techniques or biomarkers available to detect DOX-cardiotoxicity before functional decline. Mitochondrial dysfunction is thought to be a key factor driving functional decline, though real-time metabolic fluxes have never been assessed in DOX-cardiotoxicity. Hyperpolarized magnetic resonance imaging (MRI) can assess real-time metabolic fluxes in vivo. Here we show that cardiac functional decline in a clinically relevant rat-model of DOX-HF is preceded by a change in oxidative mitochondrial carbohydrate metabolism, measured by hyperpolarized MRI. The decreased metabolic fluxes were predominantly due to mitochondrial loss and additional mitochondrial dysfunction, and not, as widely assumed hitherto, to oxidative stress. Since hyperpolarized MRI has been successfully translated into clinical trials this opens up the potential to test cancer patients receiving DOX for early signs of cardiotoxicity.
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29 schema:keywords DOX-HF
30 additional mitochondrial dysfunction
31 agents
32 biomarkers
33 cancer patients
34 carbohydrate metabolism
35 cardiac functional decline
36 cardiac metabolic signature
37 cardiotoxic side effects
38 cardiotoxicity
39 changes
40 chemotherapeutic agents
41 clinical imaging techniques
42 clinical trials
43 congestive heart failure
44 decline
45 decreased metabolic fluxes
46 detection
47 doxorubicin
48 dysfunction
49 early detection
50 early signs
51 effect
52 factors
53 failure
54 flux
55 functional decline
56 heart failure
57 hitherto
58 imaging
59 imaging techniques
60 key factors
61 loss
62 magnetic resonance imaging
63 metabolic flux
64 metabolic signatures
65 metabolism
66 mitochondrial carbohydrate metabolism
67 mitochondrial dysfunction
68 mitochondrial loss
69 oxidative mitochondrial carbohydrate metabolism
70 patients
71 potential
72 rats
73 real-time metabolic fluxes
74 resonance imaging
75 serious cardiotoxic side effects
76 side effects
77 signatures
78 signs
79 stress
80 technique
81 trials
82 vivo
83 schema:name Early detection of doxorubicin-induced cardiotoxicity in rats by its cardiac metabolic signature assessed with hyperpolarized MRI
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