Novel insights into bicuspid aortic valve (BAV) aortopathy: Long non-coding RNAs TUG1 and MIAT are differentially expressed in BAV ascending aortas

Abstract

BackgroundWhilst a combination of genetically mediated vulnerability and hemodynamic insult is suspected to contribute to bicuspid aortic valve (BAV) aortopathy, the underlying pathophysiological mechanisms are poorly understood. MethodsUtilizing RT-qPCR, we compared the expression of 28 potentially relevant long non-coding RNA (lncRNA) in aortic tissue from BAV patients undergoing aortic surgery for aortopathy, to healthy controls. Relative lncRNA expression was measured using ΔΔCT, with fold-change calculated as RQ=2−ΔΔCT. ResultsWhen comparing samples from BAV patients (n=29, males n=25; median age 58 years, Q1-Q3 51–65, maximum aortic dimension 50±5 mm) with healthy controls (n=7; males n=4, P=.12; median age 39 years, Q1-Q3 18-47, P=.001), there were two differentially expressed lncRNA: TUG1 expression was significantly lower in BAV aortic tissue (RQ 0.59, 95% CI 0.50–0.69, P=.02), whilst MIAT expression was significantly higher (RQ 2.87, 95% CI 1.96–4.20, P=.01). Sensitivity analysis including only patients with normal BAV function showed similar trends of differential expression of TUG1 (RQ 0.69, 95% CI 0.50-0.90, P=.29) and MIAT (RQ 2.55, 95% CI 1.21-5.36, P=.29) compared to controls. ConclusionsLncRNA TUG1 and MIAT are differentially expressed in BAV aortopathy compared to healthy controls, independent of BAV hemodynamics. Aberrant lncRNA expression may be involved in the pathogenesis of BAV aortopathy