The fibrillin-1 hypomorphic mgR/mgR murine model of Marfan syndrome shows severe elastolysis in all segments of the aorta Simon Schwill, Philipp Seppelt,

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Presentation transcript:

The fibrillin-1 hypomorphic mgR/mgR murine model of Marfan syndrome shows severe elastolysis in all segments of the aorta Simon Schwill, Philipp Seppelt, Johannes Grünhagen, Claus-Eric Ott, MD, Manfred Jugold, PhD, Arjang Ruhparwar, MD, PhD, Peter N. Robinson, MD, PhD, Matthias Karck, MD, PhD, Klaus Kallenbach, MD, PhD Journal of Vascular Surgery Volume 57, Issue 6, Pages 1628-1636.e3 (June 2013) DOI: 10.1016/j.jvs.2012.10.007 Copyright © 2013 Society for Vascular Surgery Terms and Conditions

Fig 1 Schematic drawing of the mouse aorta. The ascending (A), descending thoracic (B), pararenal abdominal (C), and infrarenal abdominal aorta (D) were excised, and frozen cross sections were stained with Van Gieson, alizarin red, hematoxylin-eosin, and Movat pentachrome. Journal of Vascular Surgery 2013 57, 1628-1636.e3DOI: (10.1016/j.jvs.2012.10.007) Copyright © 2013 Society for Vascular Surgery Terms and Conditions

Fig 2 A, Typical phenotype of mgR/mgR mouse presenting with severe kyphosis and rectal prolapse (arrow). B, Severe scoliosis is very common in homozygous mgR mice and is visible after median laparotomy and thoracotomy. C, In vivo computed tomographic scans emphasize deformities in the skeleton of mgR/mgR compared with wild-type (wt) mice. D, In vivo computed tomographic scans of the aorta showed aneurysm formation in the ascending aorta and severe kinking of the thoracic aorta in mgR/mgR mice, whereas no pathologic changes were found in wt mice. Journal of Vascular Surgery 2013 57, 1628-1636.e3DOI: (10.1016/j.jvs.2012.10.007) Copyright © 2013 Society for Vascular Surgery Terms and Conditions

Fig 3 Degradation of elastin layers in the aortic media can be found at the age of 14-18 weeks in all aortic segments of mgR/mgR (left) in comparison with healthy aortic sections of wild-type (wt) littermates (right). Scale bar = 20 μm, 400 × 0.05 μm per pixel. Journal of Vascular Surgery 2013 57, 1628-1636.e3DOI: (10.1016/j.jvs.2012.10.007) Copyright © 2013 Society for Vascular Surgery Terms and Conditions

Fig 4 Signs of calcification were found by alizarin red stain in segment A of mgR/mgR (A) compared with wild type (wt; B) mice. In mgR/mgR mice, Movat pentachrome (C) revealed proteolysis and infiltration of immune cells in the aortic media of the ascending aorta (original magnification, 100×), and hematoxylin-eosin staining (D) showed infiltration of immune cells in the abdominal aorta (original magnification, 400×). Journal of Vascular Surgery 2013 57, 1628-1636.e3DOI: (10.1016/j.jvs.2012.10.007) Copyright © 2013 Society for Vascular Surgery Terms and Conditions

Fig 5 Samples originating from the ascending aorta (A) and the abdominal aorta (C) were analyzed in wild-type (wt) and mgR/mgR mice. Each complementary deoxyribonucleic acid was derived from RNA (ribonucleic acid) samples of n = 4 animals. Plotted are the mean expression values of quantitative polymerase chain reaction (Q-PCR) analysis performed triplicates. Data was normalized to the mean value of wt mice in the ascending aorta. Individual values are shown as diamonds and the mean value per group as horizontal line. Gene symbols are indicated on the top of each plot. Actb and Gapdh were used as endogenous control genes and relative quantities were calculated using qBASE.25 Journal of Vascular Surgery 2013 57, 1628-1636.e3DOI: (10.1016/j.jvs.2012.10.007) Copyright © 2013 Society for Vascular Surgery Terms and Conditions