Thoracic aortopathy in Turner syndrome and the influence of bicuspid aortic valves and blood pressure: a CMR study

AbstractWe analyzed mRNA expression of X-linked inhibitor of apoptosis protein (XIAP) in patients with Turner syndrome (TS) and examined its association with phenotypic features.XIAP mRNA expression levels were investigated in 98 patients with TS in total RNA extracted from blood leucocytes by real time quantitative polymerase chain reaction.Levels of XIAP mRNA were significantly lower in patients with bicuspid aortic valves (BAV; n=13) than those without (log XIAP –1.17±0.3 vs. –0.94±0.2, p=0.002). Significantly higher expression of XIAP mRNA was seen in patients with a mosaic karyotype and renal malformations (log XIAP –0.79±0.3 vs. –1.0±0.3, p=0.03). No correlations were seen between XIAP and other manifestations.Abnormal expression of XIAP may be an important underlying mechanism in the development of BAV and renal malformations in TS. However, abnormal XIAP mRNA expression, as determined from peripheral mononuclear cells, does not appear to explain all the somatic and visceral stigmata of TS.

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Coronary anatomy in Turner syndrome versus patients with isolated bicuspid aortic valves

Heart ◽

10.1136/heartjnl-2018-313724 ◽

2018 ◽

Vol 105 (9) ◽

pp. 701-707 ◽

Cited By ~ 2

Author(s):

Wilke M C Koenraadt ◽

Hans-Marc J Siebelink ◽

Margot M Bartelings ◽

Martin J Schalij ◽

Maureen J van der Vlugt ◽

...

Keyword(s):

Turner Syndrome ◽

Main Stem ◽

Left Main ◽

Aortic Valves ◽

Coronary Anatomy ◽

Equal Distribution ◽

Left Main Stem ◽

Significant Difference ◽

Bicuspid Aortic Valves ◽

Coronary Dominance

ObjectiveVariations in coronary anatomy, like absent left main stem and left dominant coronary system, have been described in patients with Turner syndrome (TS) and in patients with bicuspid aortic valves (BAV). It is unknown whether coronary variations in TS are related to BAV and to specific BAV subtypes.AimTo compare coronary anatomy in patients with TS with/without BAV versus isolated BAV and to study BAV morphology subtypes in these groups.MethodsCoronary anatomy and BAV morphology were studied in 86 patients with TS (20 TS-BAV, 66 TS-tricuspid aortic valve) and 86 patients with isolated BAV (37±13 years vs 42±15 years, respectively) by CT.ResultsThere was no significant difference in coronary dominance between patients with TS with and without BAV (25% vs 21%, p=0.933). BAVs with fusion of right and left coronary leaflets (RL BAV) without raphe showed a high prevalence of left coronary dominance in both TS-BAV and isolated BAV (both 38%). Absent left main stem was more often seen in TS-BAV as compared with isolated BAV (10% vs 0%). All patients with TS-BAV with absent left main stem had RL BAV without raphe.ConclusionThe equal distribution of left dominance in RL BAV without raphe in TS-BAV and isolated BAV suggests that presence of left dominance is a feature of BAVs without raphe, independent of TS. Both TS and RL BAV without raphe seem independently associated with absent left main stems. Awareness of the higher incidence of particularly absent left main stems is important to avoid complications during hypothermic perfusion.

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Pericardial patch augmentation for incompetant bicuspid aortic valves at longterm

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0032-1332610 ◽

2013 ◽

Vol 61 (S 01) ◽

Author(s):

M Doss ◽

M Thudt ◽

A Miskovic ◽

A Moritz

Keyword(s):

Pericardial Patch ◽

Aortic Valves ◽

Bicuspid Aortic Valves

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Epigenetic Profiling Identifies Novel Genes for Ascending Aortic Aneurysm Formation with Bicuspid Aortic Valves

The Heart Surgery Forum ◽

10.1532/hsf.1247 ◽

2015 ◽

Vol 18 (4) ◽

pp. 134 ◽

Cited By ~ 12

Author(s):

Asad A Shah

Keyword(s):

Gene Expression ◽

Aortic Aneurysm ◽

Methylation Status ◽

Aortic Aneurysms ◽

Aortic Valves ◽

Ascending Aortic Aneurysm ◽

Novel Genes ◽

Aneurysm Formation ◽

Aortic Replacement ◽

Bicuspid Aortic Valves

Background: Bicuspid aortic valves predispose to ascending aortic aneurysms, but the mechanisms underlying this aortopathy remain incompletely characterized. We sought to identify epigenetic pathways predisposing to aneurysm formation in bicuspid patients.Methods: Ascending aortic aneurysm tissue samples were collected at the time of aortic replacement in subjects with bicuspid and trileaflet aortic valves. Genome-wide DNA methylation status was determined on DNA from tissue using the Illumina 450K methylation chip, and gene expression was profiled on the same samples using Illumina Whole-Genome DASL arrays. Gene methylation and expression were compared between bicuspid and trileaflet individuals using an unadjusted Wilcoxon rank sum test. Results: Twenty-seven probes in 9 genes showed significant differential methylation and expression (P<5.5x10-4). The top gene was protein tyrosine phosphatase, non-receptor type 22 (PTPN22), which was hypermethylated (delta beta range: +15.4 to +16.0%) and underexpressed (log 2 gene expression intensity: bicuspid 5.1 vs. trileaflet 7.9, P=2x10-5) in bicuspid patients, as compared to tricuspid patients. Numerous genes involved in cardiovascular development were also differentially methylated, but not differentially expressed, including ACTA2 (4 probes, delta beta range: -10.0 to -22.9%), which when mutated causes the syndrome of familial thoracic aortic aneurysms and dissectionsConclusions: Using an integrated, unbiased genomic approach, we have identified novel genes associated with ascending aortic aneurysms in patients with bicuspid aortic valves, modulated through epigenetic mechanisms. The top gene was PTPN22, which is involved in T-cell receptor signaling and associated with various immune disorders. These differences highlight novel potential mechanisms of aneurysm development in the bicuspid population.

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