In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 35, No. suppl_1 ( 2015-05)
Abstract:
Radiotherapy is an established therapeutic method in many different cancer types. The success of modern cancer treatment raises a new problem, namely radiotherapy-induced vascular disease (vRTx) or vasculopathy, which typically emerges in irradiated areas of the heart, neck and brain and manifests itself as coronary disease, heart failure or carotid stenosis. A chronic inflammatory response likely underlies vRTx. Like in atherosclerosis, complex biological processes such as vascular cell proliferation, remodeling, oxidative stress, and tumor growth factor β (TGF-β)-regulated nuclear factor kappa B (NF-κB) activation are involved. These processes are tightly regulated by a multitude of factors, which separately are difficult to influence. A set of miRNAs known to orchestrate these processes in other disease contexts likely also play a role in vRTx, and might be modifiable in order to treat or prevent RTx-induced vascular disease. We selected miR-29b, miR-125a, miR-126, miR-143, miR-145, miR-146a, miR-155, miR-221, miR-222, and miR-503 and determined their potential contribution to vRTx. Utilizing unique biobank material from microvascular free tissue transfer reconstructions, where irradiated (R) vascular tissue (branches from external carotid arteries and internal jugular veins) can be compared with non-irradiated control tissue (NR) within the same patient (n=10), we could precisely determine which miRNAs become deregulated after irradiation. Currently we are using a mouse model of local irradiation for further analysis and assessment of miRNA modulation effects. Apoe -/- mice are irradiated in the mediastinal area; control littermates were sham irradiated. We checked the expression of the 10 pre-selected miRNAs in R vs. NR vascular tissue (ascending and thoracic aorta). Of the 10 miRNAs, three (miR-29b up-; miR-143, miR-145 downregulated) were significantly differentially regulated between R and NR human arteries. miR-146a trended upward, but not significantly. Ongoing studies are aimed at histological analysis of mouse R vs. NR tissue, functional modulation of deregulated miRNAs in vivo to assess vRTx outcome, and in vitro assessment of miRNA expression differences in different human vascular cell lines exposed to radiation.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/atvb.35.suppl_1.556
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2015
detail.hit.zdb_id:
1494427-3
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