Abstract 18637: Differing Genetic Expression Patterns in Infants with Aortic Coarctation With Without Arch Hypoplasia
Introduction: Despite adequate repair, coarctation of the aorta (CoA) with concomitant aortic arch hypoplasia (AAH) is associated with an increased risk of hypertension. However, the mechanism(s) involved in the development of hypertension are unknown
Hypothesis: We hypothesized that the aortic arch of infants with CoA + AAH would have differences in gene expression compared to infants with CoA alone, providing insight into the pathophysiologic mechanisms leading to later hypertension.
Methods: In 14 infants (7-CoA+AAH, 7-CoA alone) we analyzed mRNA after isolating the aortic tissue from the transverse aortic arch and the aorta distal to the CoA. An Affymetrix 1.0 genome array was performed to elucidate differences in gene expression between aortic arch and distal aorta from infants with CoA+AAH vs. CoA alone. RT-PCR validated genetic differences after quantifying the fold difference in expression by normalizing the aortic arch mRNA to the distal aorta.
Results: The micro-array data identified 807 genes that were significantly expressed from within the aortic arch of infants with CoA+AAH, predominantly in vascular smooth muscle cell regulation, cell division, and development. In contrast, infants with isolated CoA without AAH, demonstrated decreased number, and different focus, of gene expression (532 genes predominately involved in cell division). RT-PCR confirmed that aortic arch hepsin expression, a gene involved in cell growth, was significantly over-expressed in infants with CoA+AAH (26.1±18 vs. 0.5±10; p=0.05).
Conclusions: Infants with CoA+AAH have differences in aortic arch gene expression compared to infants with CoA alone. We postulate that these genetic variations contribute to the pathophysiologic changes that lead to later hypertension.
Author Disclosures: M.F. Swartz: None. P. Parikh: None. J.M. Cholette: None. N. Atallah-Yunes: None. G.M. Alfieris: None.
- © 2014 by American Heart Association, Inc.