Bicuspid Aortic Valve Morphotype Correlates With Regional Antioxidant Gene Expression Profiles in the Proximal Ascending Aorta Julie A. Phillippi, PhD,

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Bicuspid Aortic Valve Morphotype Correlates With Regional Antioxidant Gene Expression Profiles in the Proximal Ascending Aorta Julie A. Phillippi, PhD, Jennifer C. Hill, MFS, Marie Billaud, PhD, Benjamin R. Green, MS, Mary P. Kotlarczyk, PhD, Thomas G. Gleason, MD The Annals of Thoracic Surgery Volume 104, Issue 1, Pages 79-87 (July 2017) DOI: 10.1016/j.athoracsur.2016.10.039 Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions

Fig 1 Expression of the superoxide dismutase isoform 1 (Sod1) gene in human ascending aorta in the (A) left (L), (B) non (N), and (C) right (R) regions (n = 76 patients). Box plots depict the median (middle line of the box), first quartile (lower line of the box) and third quartile (upper line of the box), with the whiskers representing 90th and 10th percentiles. The closed circles indicate outliers. *p < 0.05, significant from TAV-NA (normal). (BAV = bicuspid aortic valve; NA = nonaneurysmal; TAA = thoracic aortic aneurysm; TAV = tricuspid aortic valve.) The Annals of Thoracic Surgery 2017 104, 79-87DOI: (10.1016/j.athoracsur.2016.10.039) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions

Fig 2 Expression of the superoxide dismutase isoform 2 (Sod2) gene in human ascending aorta in the (A) left (L) (B) non (N), and (C) right (R) regions (n = 76 patients). The box plots depict the median (middle line of the box), first quartile (lower line of the box) and third quartile (upper line of the box), with the whiskers representing the 90th and 10th percentiles. The closed circles indicate outliers. *p < 0.05 significant from TAV-NA (normal). (BAV = bicuspid aortic valve; NA = nonaneurysmal; TAA = thoracic aortic aneurysm; TAV = tricuspid aortic valve.) The Annals of Thoracic Surgery 2017 104, 79-87DOI: (10.1016/j.athoracsur.2016.10.039) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions

Fig 3 Expression of the superoxide dismutase isoform 3 (Sod3) gene in human ascending aorta in the (A) left (L), (B) non (N), and (C) right (R) regions (n = 76 patients). The box plots depict the median (middle line of the box), first quartile (lower line of the box) and third quartile (upper line of the box), with whiskers bars representing 90th and 10th percentiles. The closed circles indicate outliers. * p < 0.05, significant from TAV-NA (normal). (BAV = bicuspid aortic valve; NA = nonaneurysmal; TAA = thoracic aortic aneurysm; TAV = tricuspid aortic valve.) The Annals of Thoracic Surgery 2017 104, 79-87DOI: (10.1016/j.athoracsur.2016.10.039) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions

Fig 4 Expression of the superoxide dismutase (Sod) gene in bicuspid aortic valve (BAV) specimens by disease state. Total RNA from human ascending aorta was analyzed using real-time quantitative polymerase chain reaction. Results are shown for left (L), non (N), and right (R) regions each for (A) Sod1, (B) Sod2, and (C) Sod3. *p < 0.05, significant from TAV-NA (normal). (NA = nonaneurysmal; TAA = thoracic aortic aneurysm; TAV = tricuspid aortic valve.) The Annals of Thoracic Surgery 2017 104, 79-87DOI: (10.1016/j.athoracsur.2016.10.039) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions

Fig 5 Schematic of overall findings. Prevalence of the bicuspid aortic valve (BAV) morphotype is displayed as a percentage of BAV patients (n = 157) presenting for elective replacement of a nonaneurysmal (NA) aortic valve or aortic replacement due to thoracic aortic aneurysm (TAA), or both. Sod transcriptions represent regionalized specimens from 74 patients, of which 44 BAV patients were a subset. Findings for BAV specimens are summarized as upregulation (↑) or downregulation (↓) by left (L), right (R), or non (N) region and aneurysmal status (NA or TAA) compared with NA tricuspid aortic valve (TAV) patients (TAV-NA). No change in expression when compared with TAV-NA is denoted by a dash (–). Sod transcript expression is unknown (ukn) for all patients with type 1 L/N morphotype, type 0 aneurysmal patients, and NA type 0, type 1 R/N, and type 2 patients due to low prevalence and sample sizes available. The Annals of Thoracic Surgery 2017 104, 79-87DOI: (10.1016/j.athoracsur.2016.10.039) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions