587 Role of Long Noncoding RNAs in the Pathogenesis of Thoracic Aortic Aneurysms in Marfan Syndrome

Marfan syndrome (MFS) is a connective tissue disorder with early morbidity and mortality due to thoracic aortic aneurysm (TAA). Long noncoding RNAs (lncRNA) are targetable epigenetic disease modifiers associated with the pathogenesis of MFS, such as abnormal TGF-β signalling. Hypoxia due to obstructive sleep apnoea (OSA) has also been proposed as a potential mediator of TAA development. We aim to determine if hypoxia is associated with lncRNA expression, and together, involved in TAA in MFS. The expression of 57 lncRNAs involved in these relevant pathways was determined using RT-qPCR of RNA extracted from aortic tissue of MFS patients (n=9; M:F 7:2) and then compared to normal healthy controls (n=5; M:F 2:3). Hypoxia was further assessed by immunohistochemistry of HIF-1α in paraffin embedded sections of matched MFS aortic tissue, compared to commercially purchased controls (n=2). Overall, there was no significant differences in lncRNA or HIF-1α expression in MFS aortic tissue when compared to control. However, exploratory subgroup analysis within the MFS cohort identified that MIAT, HAS2-AS1 and UBA6-AS1 were significantly altered as a function of patient age and HIF-1α expression, revealing a potential role of these lncRNAs and hypoxia within MFS. Specifically, MIAT expression decreased with age, while HAS2-AS1 and UBA6-AS1 were associated inversely and directly with HIF-1α expression, respectively. These exploratory data indicate that there is a potential role for hypoxia in TAA formation in MFS. The observed correlation with age and possibly OSA, indicates the potential of lncRNAs as genetic targets in MFS and OSA.