New ascending aortic aneurysm model in rats reproduces main structural features of degenerative ascending thoracic aortic aneurysms in human beings Narcis.

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New ascending aortic aneurysm model in rats reproduces main structural features of degenerative ascending thoracic aortic aneurysms in human beings Narcis Costin Radu, MD, Marianne Gervais, PhD, Stéphanie Michineau, PhD, Raphaël Blanc, MD, Alexandre Fifre, PhD, Ernst Wilhelm Matthias Kirsch, MD, PhD, Eric Allaire, MD, PhD The Journal of Thoracic and Cardiovascular Surgery Volume 145, Issue 6, Pages 1627-1634 (June 2013) DOI: 10.1016/j.jtcvs.2012.07.050 Copyright © 2013 The American Association for Thoracic Surgery Terms and Conditions

Figure 1 A, Intraoperative view through the operating microscope showing the entire ascending aorta with the beginning of the brachiocephalic trunk and aortic arch at the top, before elastase treatment. B, Ascending aorta after elastase treatment. C, Angiography performed at 30-day follow-up, before death, showing thoracic aorta in a control group animal and (D), a treated animal. The Journal of Thoracic and Cardiovascular Surgery 2013 145, 1627-1634DOI: (10.1016/j.jtcvs.2012.07.050) Copyright © 2013 The American Association for Thoracic Surgery Terms and Conditions

Figure 2 A, Ascending aortic diameters measured by transthoracic ultrasounds preoperatively (elastase n = 15, control n = 6) and at 10-day (elastase n = 15, control n = 6) and 30-day (elastase n = 10, control n = 3) follow-up. The graph shows each data point and median values (horizontal line). B, Thickness of the medial layer measured by computer-assisted videomicroscopy. The graph shows median values of each experimental group (elastase n = 10, control n = 3). C, Standardization of the area of the medial layer by dividing it to the corresponding internal perimeter of the vessel. The graph shows median values of each experimental group (elastase n = 10, control n = 3). D, Standardization of the total area of vessel wall by dividing it to the corresponding internal perimeter of the vessel. The graph shows median values of each experimental group (elastase n = 10, control n = 3). E, Activation of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in the aortic wall of control (n = 3) and elastase-treated (n = 4) rats at 30-day follow-up. Representative zymogram is shown with a graph of quantitative analysis of active MMP-2 levels. Gelatin zymography detects 2 major bands corresponding to the size of proform and active form of MMP-2. *P < .05 versus control group. The Journal of Thoracic and Cardiovascular Surgery 2013 145, 1627-1634DOI: (10.1016/j.jtcvs.2012.07.050) Copyright © 2013 The American Association for Thoracic Surgery Terms and Conditions

Figure 3 Histologic sections of treated (A-D) and control (E, F) ascending aortae stained with orcein for elastic fibers (A, C, and E) and α-actin (B, D, and F). Immediately after elastase treatment, there was extensive destruction of elastic lamellae and no expression of α-smooth muscle actin (A, B). At 10-day follow-up, there were fragmented and disarrayed elastic fibers in the media and adventitia and faint expression of α-smooth muscle actin in the media but an intense expression in the adventitia (C, D). Control aortae at 10-day follow-up show normal architecture of elastic lamellae and α-smooth muscle actin expression (E, F). The Journal of Thoracic and Cardiovascular Surgery 2013 145, 1627-1634DOI: (10.1016/j.jtcvs.2012.07.050) Copyright © 2013 The American Association for Thoracic Surgery Terms and Conditions

Figure 4 A, C, and E, Sections of control aortae at 30-day follow-up and (B, D, and F) treated aortae at 30-day follow-up. Elastase treatment produced marked elastic fiber fragmentation (orcein staining [A, B]), decreased collagen in the media but increased collagen production in the adventitia (Sirius red staining [C, D]). The loss of α-smooth muscle actin expression persisted in the media of treated aortas and was accompanied by its expression in the adventitia (E, F). The Journal of Thoracic and Cardiovascular Surgery 2013 145, 1627-1634DOI: (10.1016/j.jtcvs.2012.07.050) Copyright © 2013 The American Association for Thoracic Surgery Terms and Conditions