Dataset Information

Altered DNA methylation pattern reveals epigenetic regulation of Hox genes in thoracic aortic dissection and serves as a biomarker in disease diagnosis.

ABSTRACT:

Background

Thoracic aortic dissection (TAD) is a severe disease with limited understandings in its pathogenesis. Altered DNA methylation has been revealed to be involved in many diseases etiology. Few studies have examined the role of DNA methylation in the development of TAD. This study explored alterations of the DNA methylation landscape in TAD and examined the potential role of cell-free DNA (cfDNA) methylation as a biomarker in TAD diagnosis.

Results

Ascending aortic tissues from TAD patients (Stanford type A; n = 6) and healthy controls (n = 6) were first examined via whole-genome bisulfite sequencing (WGBS). While no obvious global methylation shift was observed, numerous differentially methylated regions (DMRs) were identified, with associated genes enriched in the areas of vasculature and heart development. We further confirmed the methylation and expression changes in homeobox (Hox) clusters with 10 independent samples using bisulfite pyrosequencing and quantitative real-time PCR (qPCR). Among these, HOXA5, HOXB6 and HOXC6 were significantly down-regulated in TAD samples relative to controls. To evaluate cfDNA methylation pattern as a biomarker in TAD diagnosis, cfDNA from TAD patients (Stanford type A; n = 7) and healthy controls (n = 4) were examined by WGBS. A prediction model was built using DMRs identified previously from aortic tissues on methylation data from cfDNA. Both high sensitivity (86%) and specificity (75%) were achieved in patient classification (AUC = 0.96).

Conclusions

These findings showed an altered epigenetic regulation in TAD patients. This altered epigenetic regulation and subsequent altered expression of genes associated with vasculature and heart development, such as Hox family genes, may contribute to the loss of aortic integrity and TAD pathogenesis. Additionally, the cfDNA methylation in TAD was highly disease specific, which can be used as a non-invasive biomarker for disease prediction.

SUBMITTER: Liu P

PROVIDER: S-EPMC8186232 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundRetrograde type A aortic dissection (RTAD) is a rare but life-threatening complication after thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD). A graft inversion technique was applied to distal anastomosis in total arch replacement for this complicated dissection. We reviewed our results of the processing for this serious complication. The aim is to evaluate the feasibility of this technology.MethodsFrom January 2013 to December 2017, 20 patients (80% male, mean age 50.9 ± 9.5 years) with retrograde type A aortic dissection after thoracic endovascular aortic repair for type B aortic dissection were scheduled for surgical treatment at our center. All patients underwent an ascending aorta and total aortic arch replacement procedure. The 20 patients were divided into two groups, 1 group involved 9 patients underwent surgery using stepwise technique; the graft inversion technique was performed in the other group containing the remaining 11 patients. The postoperative variables, including cardiopulmonary bypass time, the circulatory arrest time, the aortic cross clamp time, were analyzed. Meanwhile we also analyzed the postoperative mortality and complications to evaluate the early and mid-term outcomes of surgical treatment for RTAD after TEVAR.ResultsIn-hospital mortality was 10% (2 of 20 patients). No patient developed postoperative paraplegia, renal failure, stroke, or distal anastomotic bleeding. Two patients developed renal insufficiency, one developed neurologic insufficiency, and one developed pulmonary infection, all of which were managed accordingly. Cardiopulmonary bypass (CPB) time, and circulatory arrest time were significantly shorter in the graft inversion group than in the stepwise group (165.8 ± 37.9 min versus 206.1 ± 46.8 min, p<0.05; 34.5 ± 5.6 min versus 42.4 ± 9.5 min, p<0.05, respectively). The 18 survivors had a mean follow-up of 25.8 ± 18.2 months, and all patients remained alive and well.ConclusionGraft inversion can enable a secure distal anastomosis under good surgical exposure, resulting in reduced durations of CPB, and circulatory arrest for RTAD after TEVAR. Surgical treatment could be a safe alternative for treatment of this patients.