TY - JOUR
T1 - Evidence for altered post-transcriptional regulation of TGF-β signaling in Marfan syndrome
AU - Robertson, E.
AU - Lu, Y.
AU - Lai, D.
AU - Kekic, M.
AU - Hambly, B.
AU - Jeremy, R.
PY - 2015
Y1 - 2015
N2 - Thoracic aortic aneurysms in Marfan syndrome (MFS) are associated with an increase in circulating TGF-. This indicates that, in addition to the fibrillin mutation, there is also altered signaling influencing aneurysm formation. Changes in post-transcriptional modifiers, such as microRNA, are systemic adaptive responses that can effect signaling protein expression. We hypothesised that there is post-transcriptional regulation of gene expression for signaling proteins that interact with the variant fibrillin in MFS. Total RNA was isolated from whole blood, collected using RNA preservation solution from 13 MFS patients with aortic dilatation (6F, 7M; Ao Diameter 44.4±6.0mm) and 10 controls (5F, 5M; Ao Diameter 32.3±5mm). 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 control. In MFS patients, 30 microRNA were significantly altered (22 up regulated, 8 down regulated). Of these, six have previously been implicated in the TGF- signaling pathway (miR 17, miR 146b, miR 93*, miR 106b*, miR 376c, miR 487a). Three are implicated in GATA4 signaling and cardiac development (miR 144*, miR 26B, miR19-b1), and four are implicated in either myocardial injury or vascular development (miR 208, miR 374, miR 126, miR 486). This study is the first to provide evidence for adaptive responses at the post-transcriptional level of gene expression, which may modulate aneurysm development and changes in ventricular function in MFS.
AB - Thoracic aortic aneurysms in Marfan syndrome (MFS) are associated with an increase in circulating TGF-. This indicates that, in addition to the fibrillin mutation, there is also altered signaling influencing aneurysm formation. Changes in post-transcriptional modifiers, such as microRNA, are systemic adaptive responses that can effect signaling protein expression. We hypothesised that there is post-transcriptional regulation of gene expression for signaling proteins that interact with the variant fibrillin in MFS. Total RNA was isolated from whole blood, collected using RNA preservation solution from 13 MFS patients with aortic dilatation (6F, 7M; Ao Diameter 44.4±6.0mm) and 10 controls (5F, 5M; Ao Diameter 32.3±5mm). 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 control. In MFS patients, 30 microRNA were significantly altered (22 up regulated, 8 down regulated). Of these, six have previously been implicated in the TGF- signaling pathway (miR 17, miR 146b, miR 93*, miR 106b*, miR 376c, miR 487a). Three are implicated in GATA4 signaling and cardiac development (miR 144*, miR 26B, miR19-b1), and four are implicated in either myocardial injury or vascular development (miR 208, miR 374, miR 126, miR 486). This study is the first to provide evidence for adaptive responses at the post-transcriptional level of gene expression, which may modulate aneurysm development and changes in ventricular function in MFS.
KW - Marfan syndrome
KW - thoracic arteries
KW - aneurysms
UR - https://hdl.handle.net/1959.7/uws:58257
U2 - 10.1016/j.hlc.2015.06.672
DO - 10.1016/j.hlc.2015.06.672
M3 - Article
SN - 1443-9506
VL - 24
SP - S401-S402
JO - Heart , Lung and Circulation
JF - Heart , Lung and Circulation
IS - Suppl. 3
ER -