Aorta-specific DNA methylation patterns in cell-free DNA from patients with bicuspid aortic valve-associated aortopathy

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dc.contributor.authorMaredia, Ashna
dc.contributor.authorGuzzardi, David
dc.contributor.authorAleinati, Mohammad
dc.contributor.authorIqbal, Fatima
dc.contributor.authorKhaira, Arshroop
dc.contributor.authorMadhu, Aiswarya
dc.contributor.authorWang, Xuemei
dc.contributor.authorBarker, Alex J.
dc.contributor.authorMcCarthy, Patrick M.
dc.contributor.authorFedak, Paul W. M.
dc.contributor.authorGreenway, Steven C.
dc.date.accessioned2021-08-01T00:03:18Z
dc.date.available2021-08-01T00:03:18Z
dc.date.issued2021-07-28
dc.date.updated2021-08-01T00:03:17Z
dc.description.abstractAbstract Background The dilation of the aorta that occurs as a consequence of a congenitally bicuspid aortic valve (BAV) is associated with a risk of dissection, aneurysm or rupture. With progressive aortopathy, surgery is often recommended, but current patient selection strategies have limitations. A blood-based assay to identify those who would most benefit from prophylactic surgery would be an important medical advance. In a proof-of-concept study, we sought to identify aorta-specific differentially methylated regions (DMRs) detectable in plasma cell-free DNA (cfDNA) obtained from patients undergoing surgery for BAV-associated aortopathy. Methods We used bioinformatics and publicly available human methylomes to identify aorta-specific DMRs. We used data from 4D-flow cardiac magnetic resonance imaging to identify regions of elevated aortic wall shear stress (WSS) in patients with BAV-associated aortopathy undergoing surgery and correlated WSS regions with aortic tissue cell death assessed using TUNEL staining. Cell-free DNA was isolated from patient plasma, and levels of candidate DMRs were correlated with aortic diameter and aortic wall cell death. Results Aortic wall cell death was not associated with maximal aortic diameter but was significantly associated with elevated WSS. We identified 24 candidate aorta-specific DMRs and selected 4 for further study. A DMR on chromosome 11 was specific for the aorta and correlated significantly with aortic wall cell death. Plasma levels of total and aorta-specific cfDNA did not correlate with aortic diameter. Conclusions In a cohort of patients undergoing surgery for BAV-associated aortopathy, elevated WSS created by abnormal flow hemodynamics was associated with increased aortic wall cell death which supports the use of aorta-specific cfDNA as a potential tool to identify aortopathy and stratify patient risk.
dc.identifier.citationClinical Epigenetics. 2021 Jul 28;13(1):147
dc.identifier.doihttps://doi.org/10.1186/s13148-021-01137-y
dc.identifier.urihttp://hdl.handle.net/1880/113684
dc.language.rfc3066en
dc.rights.holderThe Author(s)
dc.titleAorta-specific DNA methylation patterns in cell-free DNA from patients with bicuspid aortic valve-associated aortopathy
dc.typeJournal Article
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