Aorta-specific DNA methylation patterns in cell-free DNA from patients with bicuspid aortic valve-associated aortopathy.
Aorta-specific DNA methylation patterns in cell-free DNA from patients with bicuspid aortic valve-associated aortopathy.
复制标题
DOI：
10.1186/s13148-021-01137-y
复制
发表时间：
2021-07-28
影响因子：
5.7
通讯作者：
Greenway SC
中科院分区：
文献类型：
--
作者：
Maredia A;Guzzardi D;Aleinati M;Iqbal F;Khaira A;Madhu A;Wang X;Barker AJ;McCarthy PM;Fedak PWM;Greenway SC
由于先天性二叶式主动脉瓣（BAV）而发生的主动脉扩张与夹层、动脉瘤或破裂的风险相关。对于进行性腰椎病，通常建议手术，但目前的患者选择策略有局限性。一种基于血液的检测方法来确定那些从预防性手术中受益最大的人将是一个重要的医学进步。在一项概念验证研究中，我们试图鉴定从接受BAV相关性脊椎病手术的患者中获得的血浆游离DNA（cfDNA）中可检测到的脊椎特异性差异甲基化区域（DMR）。我们使用生物信息学和公开可用的人类甲基化组来鉴定拟南芥特异性DMR。我们使用4D血流心脏磁共振成像的数据来确定接受手术的BAV相关性动脉病患者的主动脉壁剪切应力（WSS）升高区域，并使用TUNEL染色评估WSS区域与主动脉组织细胞死亡的相关性。从患者血浆中分离无细胞DNA，候选DMR水平与主动脉直径和主动脉壁细胞死亡相关。主动脉壁细胞死亡与主动脉最大直径无关，但与WSS升高显著相关。我们确定了24个候选的结核特异性DMR，并选择了4个进行进一步研究。11号染色体上的DMR对主动脉是特异性的，并且与主动脉壁细胞死亡显著相关。血浆总cfDNA水平和主动脉特异性cfDNA水平与主动脉直径无关。在因BAV相关动脉粥样硬化病接受手术的患者队列中，异常血流动力学导致的WSS升高与主动脉壁细胞死亡增加相关，这支持使用动脉粥样硬化特异性cfDNA作为识别动脉粥样硬化病和分层患者风险的潜在工具。在线版本包含补充材料，可通过10.1186/s13148-021-01137-y获得。
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. 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. 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. 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. The online version contains supplementary material available at 10.1186/s13148-021-01137-y.
登录
查看更多内容
影响因子：
5.6
作者：
Grabuschnig S;Bronkhorst AJ;Holdenrieder S;Rosales Rodriguez I;Schliep KP;Schwendenwein D;Ungerer V;Sensen CW
通讯作者：
Sensen CW
双脊肉主动脉瓣疾病的手术治疗：知识差距和研究观点。
影响因子：
6
作者：
Della Corte, Alessandro;Body, Simon C.;Booher, Anna M.;Schaefers, Hans-Joachim;Milewski, Rita K.;Michelena, Hector I.;Evangelista, Arturo;Pibarot, Philippe;Mathieu, Patrick;Limongelli, Giuseppe;Shekar, Prem S.;Aranki, Sary F.;Ballotta, Andrea;Di Benedetto, Giuseppe;Sakalihasan, Natzi;Nappi, Gianantonio;Eagle, Kim A.;Bavaria, Joseph E.;Frigiola, Alessandro;Sundt, Thoralf M.
通讯作者：
Sundt, Thoralf M.
影响因子：
39.3
作者：
Erbel, Raimund;Aboyans, Victor;Vrints, Christiaan J. M.
通讯作者：
Vrints, Christiaan J. M.
影响因子：
4
作者：
Liu J;Shar JA;Sucosky P
通讯作者：
Sucosky P
影响因子：
37.8
作者：
Nataatmadja, M;West, M;Watanabe, T
通讯作者：
Watanabe, T