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Spatial Gene Expression Changes in the Mouse Heart After Base-Targeted Irradiation.

Gerard M Walls¹, Mihaela Ghita², Rachel Queen³

¹Patrick G Johnston Centre for Cancer Research, Queen's University Belfast, Northern Ireland; Cancer Centre Belfast City Hospital, Belfast Health & Social Care Trust, Belfast, Northern Ireland.

International Journal of Radiation Oncology, Biology, Physics

|August 19, 2022

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Radiation cardiotoxicity is a risk for cancer patients. This study reveals distinct gene expression changes in the irradiated heart base, offering targets for new treatments and safer radiation doses.

Area of Science:

Cardiology
Radiation Oncology
Genomics

Background:

Radiation cardiotoxicity (RC) is a significant concern for patients undergoing thoracic cancer treatment.
The heart's response to radiation is not uniform, with the heart base being particularly sensitive and driving RC.

Purpose of the Study:

To investigate late gene expression changes in a mouse model using spatial transcriptomics.
To characterize regional radiosensitivity within the heart base after irradiation.

Main Methods:

A mouse model was used, with one mouse receiving 16 Gy irradiation to the heart base and another sham-irradiated.
Echocardiography was performed, followed by whole-heart collection at 30 weeks for spatial transcriptomic analysis.
Gene expression profiles were mapped and compared across different cardiac regions.

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Main Results:

Irradiation of the heart base led to reduced ejection fraction at 30 weeks.
Significantly more gene expression changes were observed in irradiated versus non-irradiated regions.
Specific cardiac structures like the atria and vasculature showed varied transcriptomic responses, affecting extracellular matrix, circulatory, neuronal, and contractility functions.

Conclusions:

This study provides the first spatially resolved gene expression data in irradiated heart tissues.
Understanding the regional radiation response aids in comprehending heart base radiosensitivity.
Findings can inform the development of targeted therapies and biologically relevant radiation dose constraints.