P4.03 APOPTOSIS IN THE MEDIA OF THE AORTIC WALL AND ITS RELATIONSHIP WITH AORTIC VALVE MORPHOLOGY IN AORTIC DILATATION

• Main Authors: H. Edwards, J. Dargan, L. Elliot, A. Modi, S. Ohri, P. Townsend
• Format: Article
• Language: English
• Published: Atlantis Press 2013-11-01
• Series: Artery Research
• Online Access: https://www.atlantis-press.com/article/125939008/view
• ISSN: 1876-4401

Background: The aortic valve is normally tricuspid but may vary in that it can be made up of 1, 2 or 4 leaflets with each of these often associated with aortopathy, most commonly aortic dilatation. In patients with a bicuspid valve this association has been explained in part by molecular changes taking place in the smooth muscle cells of the aortic media resulting in their apoptosis. Objectives: To investigate changes in apoptosis and their genetic regulators that occur in the aortic media of patients with aortic dilatation and whether this differs with different aortic valve configurations. Methods: Aortic wall samples were collected from patients with unicuspid, bicuspid, tricuspid and quadricuspid aortic valve morphology. Samples underwent homogenisation and were then analysed for a number of apoptotic markers and their genetic regulators using western blot and rt-PCR. Results: Cleaved caspase 3 expression is increased in the aortic media of both the unicuspid (1.1 μm2) and bicuspid (0.42 μm2) aortic valve samples as compared to the tricuspid (0.060 μm2) sample. Relative gene expression of P53:BCL-XL >1 in the aortic media of unicuspid and bicuspid aortic valves whilst p53:BCL-XL<1 in the media of the tricuspid sample. Conclusion: Cleaved caspase 3 assay demonstrates that smooth muscle cell apoptosis is increased in the dilated aortic media of unicuspid and bicuspid aortic valves as compared to that of the tricuspid aortic valve. This increase in apoptosis is mediated by an increase in the ratio of proapoptotic p53 to antiapoptotic BCL-XL and may explain the association between abnormal valve morphology and aortic dilatation.