MiR-145 expression and rare NOTCH1 variants in bicuspid aortic valve-associated aortopathy.
Evaldas GirdauskasJohannes PetersenNiklas NeumannMartin UngelenkIngo KurthHermann ReichenspurnerTanja ZellerPublished in: PloS one (2018)
MicroRNAs (miRNAs) may serve as elegant tool to improve risk stratification in bicuspid aortic valve (BAV)-associated aortopathy. However, the exact pathogenetic pathway by which miRNAs impact aortopathy progression is unknown. Herewith, we aimed to analyze the association between circulating miRNAs and rare variants of aortopathy-related genes. 63 BAV patients (mean age 47.3±11.3 years, 92% male) with a root dilatation phenotype, who underwent aortic valve+/-proximal aortic surgery at a single institution (mean post-AVR follow-up 10.3±6.9 years) were analyzed. A custom-made HaloPlex HS panel including 20 aortopathy-related genes was used for the genetic testing. miRNAs were extracted from whole blood and miRNA analysis was performed using miRNA-specific assay. Study endpoint was the association between circulating miRNAs and rare genetic variants in the aortopathy gene panel. The study cohort was divided into a subgroup with rare variants vs. a subgroup without rare variants based on the presence of rare variants in the respective genes (i.e., at least one variant present). The genetic analysis yielded n = 6 potentially and likely pathogenic rare variants within the NOTCH1 gene as being the most common finding. Univariate analysis between blood miRNAs and NOTCH1 variants revealed a significantly lower expression of miR-145 in the subgroup of patients with NOTCH1 variants vs. those without NOTCH1 variants (i.e., delta Ct 4.95±0.74 vs. delta Ct 5.57±0.78, p = 0.04). Our preliminary data demonstrate a significant association between blood miR-145 expression and the presence of rare NOTCH1 variants. This association may be indicative of a specific pathogenetic pathway in the development of genetically-triggered bicuspid aortopathy.
Keyphrases
- aortic valve
- copy number
- aortic stenosis
- transcatheter aortic valve replacement
- aortic valve replacement
- transcatheter aortic valve implantation
- cell proliferation
- genome wide
- poor prognosis
- computed tomography
- end stage renal disease
- ejection fraction
- randomized controlled trial
- chronic kidney disease
- peritoneal dialysis
- coronary artery disease
- magnetic resonance imaging
- prognostic factors
- single cell
- magnetic resonance
- newly diagnosed
- contrast enhanced
- acute coronary syndrome
- binding protein
- patient reported outcomes
- density functional theory
- coronary artery bypass