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Subramanian, V. ; Seemann, I.* ; Merl-Pham, J. ; Hauck, S.M. ; Stewart, F.* ; Atkinson, M.J. ; Tapio, S. ; Azimzadeh, O.

The role of TGF beta and PPAR alpha signalling pathways in radiation response of locally exposed heart: Integrated global transcriptomics and proteomics analysis.

J. Proteome Res. 16, 307-318 (2017)
Postprint Forschungsdaten DOI PMC
Open Access Green
Epidemiological data from patients undergoing radiotherapy for thoracic tumours clearly show the damaging effect of ionising radiation on cardiovascular system. The long-term impairment of heart function and structure after local high-dose irradiation is associated with systemic inflammatory response, contraction impairment, microvascular damage and cardiac fibrosis. The goal of the present study was to investigate molecular mechanisms involved in this process. C57BL/6J mice received a single X-ray dose of 16 Gy given locally to the heart at the age of 8 weeks. Radiation-induced changes in the heart transcriptome and proteome were investigated 40 weeks after the exposure. The omics data were analysed by bioinformatics tools and validated by immunoblotting. Integrated network analysis of transcriptomics and proteomics data elucidated the signalling pathways that were similarly affected at gene and protein level. Analysis showed induction of transforming growth factor (TGF) beta signalling but inactivation of peroxisome proliferator-activated receptor (PPAR) alpha signalling in irradiated heart. The putative mediator role of mitogen-activated protein kinase (MAPK) cascade linking PPAR alpha and TGF beta signalling was supported by data from immunoblotting and ELISA. This study indicates that both signalling pathways are involved in radiation-induced heart fibrosis, metabolic disordering and impaired contractility, a pathophysiological condition that is often observed in patients that received high radiation doses in thorax.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter cardiovascular disease; heart; ionizing radiation; label-free quantification; PPAR alpha; proteomics; TGF beta; transcriptomics; Activated Receptor-alpha; Myosin Heavy-chain; Breast-cancer; Long-term; Endothelial-cells; Cardiovascular-disease; Myocardial-infarction; Ionizing-radiation; Label-free; Mortality
ISSN (print) / ISBN 1535-3893
e-ISSN 1535-3907
Zeitschrift Journal of Proteome Research
Quellenangaben Band: 16, Heft: 1, Seiten: 307-318 Artikelnummer: , Supplement: ,
Verlag American Chemical Society (ACS)
Verlagsort Washington
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Radiation Biology (ISB)
CF Metabolomics & Proteomics (CF-MPC)