PXD006888

PXD006888 is an original dataset announced via ProteomeXchange.

Title	Cardiac Metabolic Deregulation Induced by the Tyrosine Kinase Receptor Inhibitor Sunitinib is rescued by Endothelin Receptor Antagonism
Description	The growing field of cardio-oncology addresses the side effects of cancer treatment on the cardiovascular system. Here, we explored the cardiotoxicity of the antiangiogenic therapy, sunitinib, in the mouse heart from a diagnostic and therapeutic perspective. We showed that sunitinib induces an anaerobic switch of cellular metabolism within the myocardium which is associated with the development of myocardial fibrosis and reduced left ventricular ejection fraction as demonstrated by echocardiography. The capacity of positron emission tomography with [18F]fluorodeoxyglucose to detect the changes in cardiac metabolism caused by sunitinib was dependent on fasting status and duration of treatment. Pan proteomic analysis in the myocardium showed that sunitinib induced (i) an early metabolic switch with enhanced glycolysis and reduced oxidative phosphorylation, and (ii) a metabolic failure to use glucose as energy substrate, similar to the insulin resistance found in type 2 diabetes. Co-administration of macitentan, the endothelin receptor antagonist, to sunitinib-treated animals prevented both metabolic defects, restored glucose uptake and cardiac function, and prevented myocardial fibrosis. These results support the endothelin system in mediating the cardiotoxic effects of sunitinib and endothelin receptor antagonism as a potential therapeutic approach to prevent cardiotoxicity. Furthermore, metabolic and functional imaging can monitor the cardiotoxic effects and the benefits of endothelin antagonism in a theranostic approach.
HostingRepository	PRIDE
AnnounceDate	2017-07-14
AnnouncementXML	Submission_2017-08-22_05:15:35.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	François GUILLONNEAU
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2017-07-07 01:14:31	ID requested
1	2017-07-14 00:30:43	announced
⏵ 2	2017-08-22 05:15:36	announced	Updated publication reference for PubMed record(s): 28824714.

Sourdon J, Lager F, Viel T, Balvay D, Moorhouse R, Bennana E, Renault G, Tharaux PL, Dhaun N, Tavitian B, Cardiac Metabolic Deregulation Induced by the Tyrosine Kinase Receptor Inhibitor Sunitinib is rescued by Endothelin Receptor Antagonism. Theranostics, 7(11):2757-2774(2017) [pubmed]

curator keyword: Biomedical

submitter keyword: cardio-oncology, cardiotoxicity, positron emission tomography, echocardiography, endothelin, sunitinib, macitentan

Bertrand Tavitian
contact affiliation	Paris Cardiovascular Research Center (PARCC); INSERM UMR970; Université Paris Descartes; Paris, France
contact email	bertrand.tavitian@inserm.fr
lab head
François GUILLONNEAU
contact affiliation	3P5 Université Paris Descartes
contact email	francois.guillonneau@parisdescartes.fr
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/07/PXD006888

PRIDE project URI

• PRIDE
  1. PXD006888
     1. Label: PRIDE project
     2. Name: Cardiac Metabolic Deregulation Induced by the Tyrosine Kinase Receptor Inhibitor Sunitinib is rescued by Endothelin Receptor Antagonism