Bicuspid Aortic Valve Morphotype Correlates With Regional Antioxidant Gene Expression Profiles in the Proximal Ascending Aorta.

BACKGROUND

Bicuspid aortic valve (BAV) is associated with asymmetric dilatation of the proximal ascending aorta. We previously demonstrated increased susceptibility of smooth muscle cells to oxidative stress in the BAV-aneurysmal aorta and hypothesized that antioxidant expression is regionally defined and influenced by the BAV morphotype.

METHODS

BAV valve morphology was defined according to number of raphes: type 0 (0 raphes), type 1 (1 raphe), or type 2 (2 raphes) and by the raphe location among the left (L), right (R) or non (N) coronary cusps. Ascending aortic specimens were partitioned into three regions corresponding to the sinuses of Valsalva, denoted R, N (greater curve), and L (lesser curve). Transcripts 1, 2, and 3 from the gene expressing superoxide dismutase (Sod) were quantified in all three regions. Results were compared with aneurysmal and nonaneurysmal aortic specimens from patients with a tricuspid aortic valve.

RESULTS

Region-specific Sod1 upregulation and Sod2 downregulation were dependent on the BAV morphotype. Sod3 was uniformly downregulated in all regions in a morphotype-independent manner. Sod1 upregulation was noted in the R region of the nonaneurysmal type 1 L/R morphotype. Aortic valve regurgitation, but not stenosis, affected the expression of Sod isoforms in specimens of degenerative aneurysms.

CONCLUSIONS

Region-specific transcription profiles of Sod on the basis of BAV morphotype deepen our understanding of its associated aortopathy and provide biological insight on the asymmetric dilatation pattern. This work indicates regional differences exist in the oxidative stress biology of the proximal aortic wall, and this may lead to newer diagnostic techniques to adjudicate aortic catastrophe risk.