Potential Molecular Mechanism of Retrograde Aortic Arch Stenosis in the Hybrid Approach to Hypoplastic Left Heart Syndrome Narutoshi Hibino, MD, Mary.

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Potential Molecular Mechanism of Retrograde Aortic Arch Stenosis in the Hybrid Approach to Hypoplastic Left Heart Syndrome Narutoshi Hibino, MD, Mary J. Cismowski, PhD, Brenda Lilly, PhD, Patrick I. McConnell, MD, Toshiharu Shinoka, MD, PhD, John P. Cheatham, MD, Pamela A. Lucchesi, PhD, Mark E. Galantowicz, MD, Aaron J. Trask, PhD The Annals of Thoracic Surgery Volume 100, Issue 3, Pages 1013-1020 (September 2015) DOI: 10.1016/j.athoracsur.2015.04.125 Copyright © 2015 The Society of Thoracic Surgeons Terms and Conditions

Fig 1 Patent ductus arteriosus tissue with (+) retrograde aortic arch stenosis (RAAS) expresses increased differentiation and vascular smooth muscle cell (VSMC)-modulation markers. The cell differentiation markers (β-actin [black bars], SM22 [white bars], and calponin [light gray bars]) and signaling pathways for VSMC modulation (transforming growth factor [TGF]-β1 [red bars], Notch [blue, green, and red bars], and platelet-derived growth factor [PDGF]-B [yellow bars]) were significantly higher in the RAAS(+) group compared with the group without (–) RAAS (n = 7 to 10 per group). α-Smooth muscle actin (SMA), dark gray bar. The error bars indicate the standard error of the mean. *p < 0.05, **p < 0.01 vs RAAS(–). The Annals of Thoracic Surgery 2015 100, 1013-1020DOI: (10.1016/j.athoracsur.2015.04.125) Copyright © 2015 The Society of Thoracic Surgeons Terms and Conditions

Fig 2 Patent ductus arteriosus tissue with (+) retrograde aortic arch stenosis (RAAS) exhibits signs of proliferation compared with tissue without (–) RAAS. Cell proliferation marker Ki67 (purple bars) were increased and cell cycle marker p27Kip1 (gray bars) were decreased, although they did not achieve statistical significance (n = 7 to 10 per group). Cyclin c1, white bars; p21Waf, red bars; proliferating cell nuclear antigen (PCNA), dark gray bars, The error bars indicate standard error of the mean. The Annals of Thoracic Surgery 2015 100, 1013-1020DOI: (10.1016/j.athoracsur.2015.04.125) Copyright © 2015 The Society of Thoracic Surgeons Terms and Conditions