Detection of early radiation-induced heart disease
Session type: Poster / e-Poster / Silent Theatre session
Breast cancer (BC) survivors are at increased risk of significant cardiovascular (CV) morbidity 10-years post-radiotherapy (RTH)(1,2). An underlying mechanism is thought to be premature CV ageing. We aimed to detect sub-clinical cardiac damage (with MRI and/or microRNA) and correlate these with in vitro markers of biological ageing. Plasma microRNA29c has shown to be a novel biomarker of an unfit heart(3) and is involved in the downstream processing of Mcl-1, an anti-apoptotic protein and the COL2A1 gene coding for type II collagen.
10 BC patients receiving adjuvant left-sided RTH underwent cardiac MRI and in vitro assays (Sub-G1 peak assay (AR), comet assay, telomere length, oxidative stress measurement) before treatment, six-weeks and one-year post-treatment. These assays were replicated, along with microRNA profiling in 25 BC patients pre and 6-weeks post-RTH. MicroRNA profiling was also performed on cardiac tissue and plasma samples from 24 female BALB/c mice after direct and sham whole body X-ray irradiation.
Cardiac MRI analysis showed no definitive changes post-RTH.
There was a reduction in the AR (P=0.002), increase in comet tail (P=0.033) and urinary 8-oxo-DG (P=0.031) at 6-weeks post-RTH, however telomere length showed no significant changes. These assays had returned to pre-treatment levels at one-year post-RTH.
Mouse models showed downregulation of MicroRNA29c levels post-RTH in both cardiac tissue (P=0.046) and plasma (P=0.02), and upregulation of Mcl-1 in cardiac tissue (P=0.001). There was a dose correlation response between radiation exposure to cardiac tissue and the reduction in miRNA29c. We have shown that this reduction in MiRNA29c can also be detected in left-sided BC patients six-weeks post-RTH (P=0.002).
MiRNA29c may be an early indicator of radiation-induced heart disease (RIHD), and shows high specificity to direct cardiac irradiation. Downstream microRNA expression changes on Mcl-1 and COL2A1 provide a potential mechanistic pathway for RIHD through a failure of apoptosis and increased cardiac tissue fibrosis.