Abstract 18889: Circulating microRNA Implicated in the TGF-β Signalling Pathway are Altered in Marfan Syndrome
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<0.05) compared to controls. microRNA that were identified as significantly altered were then validated with qPCR using targeted primers on an additional 33 MFS patients (15F, 21M; Ao Diameter 44.2±5.0mm; Age 37±13yrs).
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.
Author Disclosures: E.N. Robertson: None. Y. Lu: None. A. Sahagian: None. D. Lai: None. M. Kekic: None. B. Hambly: None. R. Jeremy: None.
- © 2015 by American Heart Association, Inc.