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Interleukin-6 Receptor Inhibition Prevents Descending Thoracic Aortic Aneurysm Formation
Nicolas H. Pope, MD, Morgan Salmon, PhD, William F. Johnston, MD, Guanyi Lu, MD, PhD, Christine L. Lau, MD, Gilbert R. Upchurch, MD, Gorav Ailawadi, MD The Annals of Thoracic Surgery Volume 100, Issue 5, Pages (November 2015) DOI: /j.athoracsur Copyright © 2015 The Society of Thoracic Surgeons Terms and Conditions
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Fig 1 (A) Aortic dilation days after topical treatment with elastase (n = 5 per group per timepoint). (Red line = thoracic aortic aneurysm [TAA] elastase; blue line = abdominal aortic aneurysm [AAA] elastase; black line = TAA saline; green line = AAA saline.) (B) Murine TAA interleukin-6 (IL-6) peaked higher and remained elevated longer than AAA, by enzyme-linked immunosorbent assay (ELISA [p < ]). (Red line = TAA elastase; blue line = AAA elastase.) Murine thoracic aortic (C) IL-6 (p = ), (D) CXCL-13 (p = ), and (E) matrix metalloprotease-9 (MMP-9 [p = 0.001]) were significantly elevated in elastase-treated mice as compared with saline-treated TAA and saline- or elastase-treated AAA. The Annals of Thoracic Surgery , DOI: ( /j.athoracsur ) Copyright © 2015 The Society of Thoracic Surgeons Terms and Conditions
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Fig 2 (A) Aortic dilation in wild type (WT) mice (n = 7 per group) and interleukin-6 knockout (IL-6KO) mice (n = 7 per group) after thoracic aortic aneurysmal (TAA) or abdominal aortic aneurysmal (AAA) application of topical elastase. *p = The IL-6KO mice had significantly smaller TAA compared with WT controls (WT 100.1% versus IL-6KO 76.5%, p = ). There was no significant difference between WT and IL-6KO AAA (WT 95.8%, IL-6KO 99.1, p = 0.73). (B) Left panels, WT TAA; right panels, IL-6KO TAA (original magnification). Elastin was preserved in IL-6KO animals without a significant difference in macrophage (Mac-2) or neutrophil (Ly-6) infiltration. (VVG = Verhoeff-Van Gieson stain.) The Annals of Thoracic Surgery , DOI: ( /j.athoracsur ) Copyright © 2015 The Society of Thoracic Surgeons Terms and Conditions
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Fig 3 (A) Treatment of wild type (WT) mice with interleukin-6 (IL-6) receptor antagonist (tocilizumab) by intraperitoneal injection before elastase treatment of the thoracic aorta. *p = Tocilizumab treatment resulted in significant decrease in aneurysm size as compared with vehicle-treated controls (tocilizumab 71.5% ± 13.2% versus vehicle 103.6% ± 20.7%, p = 0.005). (KO = knock out.) (B) Left panels, vehicle alone; right panels, tocilizumab (original magnification). Tocilizumab treatment resulted in preservation of elastin fibers (Verhoeff-Van Gieson stain [VVG]) without change in macrophage (Mac-2) infiltration. (Ly-6 = neutrophil infiltration.) The Annals of Thoracic Surgery , DOI: ( /j.athoracsur ) Copyright © 2015 The Society of Thoracic Surgeons Terms and Conditions
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Fig 4 Human thoracic and abdominal aortic cytokine content in aneurysmal and nonaneurysmal samples. (A) Interleukin-6 (IL-6) is significantly higher in thoracic aortic aneurysmal (TAA) tissue (483,206 optical density units) as compared with abdominal aortic aneurysmal (AAA) tissue (11,834 optical density units; p < ). (B) Human tissue stained for IL-6: upper panel, TAA tissue; lower panel, AAA tissue (original magnification; insets show magnified views). The TAA tissue shows significantly denser IL-6 staining than the AAA tissue (n = 4 per group). The Annals of Thoracic Surgery , DOI: ( /j.athoracsur ) Copyright © 2015 The Society of Thoracic Surgeons Terms and Conditions
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