Nicholas B. Cavanaugh, BS, Lan Qian, MD, Nicole M

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Presentation transcript:

A Novel Murine Model of Marfan Syndrome Accelerates Aortopathy and Cardiomyopathy Nicholas B. Cavanaugh, BS, Lan Qian, MD, Nicole M. Westergaard, BS, William J. Kutschke, MS, Ella J. Born, BA, Joseph W. Turek, MD, PhD The Annals of Thoracic Surgery Volume 104, Issue 2, Pages 657-665 (August 2017) DOI: 10.1016/j.athoracsur.2016.10.077 Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions

Fig 1 Transthoracic echocardiographic assessment of ascending aortic aneurysms and ventricular dilation. (A) Representative transthoracic echocardiograms of ascending aorta and left ventricle in wild-type (WT) mice (WT + vehicle), angiotensin II (Ang II)-infused WT mice (WT + Ang II), standard Marfan syndrome (MFS) mice (MFS + vehicle), and accelerated MFS mice (MFS + Ang II) at 14 days. (B) Progression of ascending aortic dilation as assessed by transthoracic echocardiography in WT (WT + vehicle [circles]), Ang II-infused WT (WT + Ang II [stars]), standard MFS (MFS + vehicle [squares]), and accelerated MFS (MFS + Ang II [triangles]) mice at 14 days. The Annals of Thoracic Surgery 2017 104, 657-665DOI: (10.1016/j.athoracsur.2016.10.077) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions

Fig 2 Decreased survivability with accelerated Marfan syndrome (MFS) model from disease-related maladies. (A) Survivability graph representing three time intervals after minipump installation (10, 14, 28 days) in wild-type (WT) mice (WT + vehicle [circles]), angiotensin II (Ang II)-infused WT mice (WT + Ang II [stars]), standard MFS mice (MFS + vehicle [squares]), and accelerated MFS mice (MFS + Ang II [triangles]). (B) A gross image displaying an ascending aortic aneurysm in an accelerated MFS model. The Annals of Thoracic Surgery 2017 104, 657-665DOI: (10.1016/j.athoracsur.2016.10.077) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions

Fig 3 Verhoeff-Van Gieson (VVG) stain assessment of aortic wall integrity. (A) Representative images of wild-type (WT) mice (WT + vehicle [Veh]), angiotensin II (Ang II)-infused WT mice (WT + Ang II), standard Marfan syndrome (MFS) mice (MFS + Veh), and accelerated MFS mice (MFS + Ang II) at 14 days through a bright field microscope at ×20 magnification. (B) Bar graph representing scored elastic fragmentation (1 to 4, where 1 = no fragmentation, 4 = highest fragmentation) differentiation in WT (WT + Veh), Ang II-infused WT (WT + Ang II), standard MFS (MFS + Veh), and accelerated MFS (MFS + Ang II) mice at 14 days (∗p < 0.05, ANOVA). The Annals of Thoracic Surgery 2017 104, 657-665DOI: (10.1016/j.athoracsur.2016.10.077) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions

Fig 4 Transthoracic echocardiographic assessment of cardiac dimensions and function. (A) Bar graph representing end-diastolic volume in wild-type (WT) mice (WT + vehicle [Veh]), angiotensin II (Ang II)-infused WT mice (WT + Ang II), standard Marfan syndrome (MFS) mice (MFS + Veh), and accelerated MFS mice (MFS + Ang II) at 14 days (∗p < 0.05, ANOVA). (B) Bar graph representing ejection fraction in WT (WT + Veh), Ang II-infused WT (WT + Ang II), standard MFS (MFS + Veh), and accelerated MFS (MFS + Ang II) mice at 14 days (∗p < 0.05, ANOVA). The Annals of Thoracic Surgery 2017 104, 657-665DOI: (10.1016/j.athoracsur.2016.10.077) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions

Fig 5 Heart mass and body mass assessment of dilated cardiomyopathy. (A) Equally scaled representative images of wild-type (WT) mice (WT + vehicle), angiotensin II (Ang II)-infused WT mice (WT + Ang II), standard Marfan syndrome (MFS) mice (MFS + vehicle), and accelerated MFS mice (MFS + Ang II) hearts after 14 days of implantation. (B) Bar graph representing heart mass (mg) to body mass (g) in WT (WT + vehicle [Veh]), Ang II-infused WT (WT + Ang II), standard MFS (MFS + Veh), and accelerated MFS (MFS + Ang II) mice at 14 days. (C) Bar graph from each treatment group of mice demonstrating heart mass (mg) to body mass (g) with varying degrees of aortic insufficiency (0 = none, 1 = mild, 2 = moderate, 3 = severe) at 14 days (∗p < 0.05, ANOVA). The Annals of Thoracic Surgery 2017 104, 657-665DOI: (10.1016/j.athoracsur.2016.10.077) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions

Fig 6 Histopathologic assessment of cardiac tissue. Representative images of sectioned cardiac hematoxylin and eosin stains of wild-type (WT) mice (WT + vehicle [Veh]), angiotensin II (Ang II)-infused WT mice (WT + Ang II), standard Marfan syndrome (MFS) mice (MFS + Veh), and accelerated MFS mice (MFS + Ang II) at 14 days through a bright field microscope at ×20 magnification. The Annals of Thoracic Surgery 2017 104, 657-665DOI: (10.1016/j.athoracsur.2016.10.077) Copyright © 2017 The Society of Thoracic Surgeons Terms and Conditions