Investigating the epigenetic basis for aortic aneurysm risk in patients with bicuspid aortic valve disease

Abstract

Background

Bicuspid aortic valve (BAV) is a common congenital cardiac malformation associated with significant morbidity, including aortic dissection and thoracic aortic aneurysms. The mechanisms underlying BAV-associated aortopathy are unknown. We aimed to identify methylation profiles in BAV patients with aortopathy and investigate associated genetic pathways.

Methods

Tissue samples from the ascending aorta were obtained from BAV patients undergoing thoracic aortic surgery. DNA methylation profiles were measured using Illumina human 850K array. Probe methylation associations were reviewed, and a regression model assessed associations with aortic dimension.

Results

Eight patients were recruited from University Hospital Southampton. Analysis revealed HEATR5A, PHLDB2, ADAMTS17, BID, and TLK1 as significantly associated genes. These genes were implicated in aortic wall remodelling through novel mechanisms identified by an unbiased, integrated epigenomic approach.

Conclusions

This study provides novel insights into epigenetic regulation in BAV-associated aortopathy. Identified genes, including HEATR5A, PHLDB2, ADAMTS17, BID, and TLK1, may contribute to aortic disease in BAV patients. Further research is needed to elucidate their mechanisms and therapeutic potential. Our findings improve understanding of the molecular basis of BAV-associated aortopathy and may inform future diagnostic and therapeutic strategies.