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Bicuspid aortic valve (BAV) is the most common congenital heart malformation, affecting 1-2% of the population. BAV is caused by fusion of two of the three aortic valve leaflets in the heart during foetal development. Progressive dilatation of the thoracic aorta, resulting in aneurysm (TAA), develops in approximately 50% of individuals with BAV, and can be fatal. The cause of BAV-TAA is undetermined, however, current understanding suggests that it is a complex interplay between genetic susceptibility and the abnormal haemodynamic stress generated by the malformed valve. Changes in the expression of post-transcriptional genetic modifiers, such as microRNA (miRNA), can alter protein expression and disrupt normal tissue function, contributing to disease. miRNA are also viable therapeutic targets with demonstrated success in disease treatment. We hypothesised that there is altered expression of miRNA in BAV-TAA tissue that contributes to TAA development. Total RNA was isolated from aortic tissue of 11 patients with BAV-TAA (Age 54 ± 12 years; M:F 10:1), and 6 normal controls with no aortic disease (Age 35 ± 18 years; M:F 4:2). RNA was reverse transcribed with primers for 818 different miRNA and qPCR was performed using Taqman® OpenArray® Human miRNA Panels. A significant difference in miRNA expression was defined as a >±2 fold change (p

Thoracic aortic aneurysms in Marfan Syndrome (MFS) caused by mutations in FBN1 are associated with altered TGF-β signaling. Regulation of gene expression can occur at the level of microRNA, which can modify signaling pathways. We hypothesized that there would be altered microRNA expression in MFS that may alter the expression of signaling proteins. Total RNA was isolated from whole blood collected in PAXgene® tubes (PreAnalytiX), from 13 MFS patients with aortic dilatation (6F, 7M; Ao Diameter 44.4±6.0mm; Age 39±12yrs) and 10 normal controls (5F, 5M; Ao Diameter 32.3±5mm; Age 34±10yrs). The RNA was reverse transcribed with Human Pool A & B primers and qPCR was performed on the subsequent cDNA using TaqMan® OpenArray® Human miRNA Panels (2454 targets) (ThermoFisher). microRNA expression was considered to be significantly altered if there was >2 fold change (p In MFS patients, the OpenArray® identified 30 microRNA were significantly altered (22 up regulated, 8 down regulated). Of these, 12 were confirmed to be altered using targeted qPCR (Graph 1). Three of these have previously been identified as modifiers of the TGF-β signaling pathway (miR 17, miR 93, miR 93*). Three were from the let-7 family (let-7e, let-7f, let-7g), which are involved in terminal cell differentiation and have been implicated in several cardiovascular disease processes. Another three have been shown to be dysregulated in various cardiovascular disease states including atherosclerotic thoracic aortic aneurysm and left ventricular hypertrophy (miR 208, miR 486, miR 378). This study provides novel evidence for adaptive responses at the post-transcriptional level of gene expression that may modulate aneurysm development in Marfan syndrome.