Wanfen Xiong, PhD, Rebecca A. Knispel, BS, Harry C

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Presentation transcript:

Doxycycline delays aneurysm rupture in a mouse model of Marfan syndrome Wanfen Xiong, PhD, Rebecca A. Knispel, BS, Harry C. Dietz, MD, Francesco Ramirez, PhD, B. Timothy Baxter, MD Journal of Vascular Surgery Volume 47, Issue 1, Pages 166-172 (January 2008) DOI: 10.1016/j.jvs.2007.09.016 Copyright © 2008 The Society for Vascular Surgery Terms and Conditions

Fig 1 The effect of doxycycline on the survival of mgR/mgR mice. Mice were treated with doxycycline (doxy) (100 mg/kg) or regular water (no doxy) daily, started at the age of 1 day. Life table analysis shows improved survival in mice treated with doxycycline (P = .0009). Journal of Vascular Surgery 2008 47, 166-172DOI: (10.1016/j.jvs.2007.09.016) Copyright © 2008 The Society for Vascular Surgery Terms and Conditions

Fig 2 Gelatin zymographic analysis of MMP-2 and MMP-9 in the mouse thoracic aortas. Mouse thoracic aortas from wild type control, mgR/mgR, and doxycycline-treated mgR/mgR mice harvested at 6 weeks of age (n = 5 mice/group). Aortic proteins were extracted and separated by electrophoresis on a 10% SDS-PAGE containing 0.8% gelatin. Band intensities (gelatinolytic activities) were measured by densitometer. Relative expression of MMP-9 and MMP-2 in wild type control, mgR/mgR, and doxycycline-treated mgR/mgR mouse aortas was analyzed. *, # P < 0.05 (*relative to wild type controls, # relative to untreated mgR/mgR mice). A representative gel is shown. Journal of Vascular Surgery 2008 47, 166-172DOI: (10.1016/j.jvs.2007.09.016) Copyright © 2008 The Society for Vascular Surgery Terms and Conditions

Fig 3 Reverse zymographic analysis of TIMP levels in the mouse thoracic aortas. Mouse thoracic aortas from wild type control, mgR/mgR, and doxycycline-treated mgR/mgR mice harvested at 6 weeks of age (n = 5 mice/group). Aortic proteins were separated by electrophoresis on a 12.5% SDS-PAGE containing 1.6% gelatin, 0.16 μg/ml MMP-2. A representative reverse zymogram shows the bands representing gelatin preserved by TIMP-1 and TIMP-2 (indicated by arrows). Band intensities were measured by densitometer. Relative expression of TIMP-1 and TIMP-2 in wild type control, mgR/mgR, and doxycycline-treated mgR/mgR mouse aortas was analyzed. Journal of Vascular Surgery 2008 47, 166-172DOI: (10.1016/j.jvs.2007.09.016) Copyright © 2008 The Society for Vascular Surgery Terms and Conditions

Fig 4 Elastic fiber degradation in the wild type (WT) and mgR/mgR mice. a, elastin breaks per field under 40x magnification in WT, mgR/mgR, and doxycycline-treated mgR/mgR mice (n = 3 aortas/group). *, # P < 0.05 (*relative to wild type controls, # relative to untreated mgR/mgR mice). b, c, and d, representative trichrome stainings of aortic tissue of WT (b), mgR/mgR (c), and doxycycline-treated mgR/mgR (d) mice at 6 weeks age. Arrows indicates breaks in elastic fibers. Journal of Vascular Surgery 2008 47, 166-172DOI: (10.1016/j.jvs.2007.09.016) Copyright © 2008 The Society for Vascular Surgery Terms and Conditions