Castration of male mice prevents the progression of established angiotensin II-induced abdominal aortic aneurysms Xuan Zhang, PhD, Sean Thatcher, PhD,

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Presentation transcript:

Castration of male mice prevents the progression of established angiotensin II-induced abdominal aortic aneurysms Xuan Zhang, PhD, Sean Thatcher, PhD, Congqing Wu, BS, Alan Daugherty, PhD, Lisa A. Cassis, PhD Journal of Vascular Surgery Volume 61, Issue 3, Pages 767-776 (March 2015) DOI: 10.1016/j.jvs.2013.11.004 Copyright © 2015 Society for Vascular Surgery Terms and Conditions

Fig 1 Castration reduces abdominal aortic lumen dilation in angiotensin II (AngII)-infused mice. A, Experimental design for quantifying effects of castration on the progression of established AngII-induced abdominal aortic aneurysms (AAAs). B, Suprarenal aorta lumen dilation at various time points after AngII infusion in sham-operated (n = 20) and castrated (n = 22) mice. The arrow indicates sham-operation or castration surgery. C, Percentage survival of mice is shown in each group from day 28 to day 84 of AngII infusion. The error bars show the standard error of the mean. ApoE−/−, apolipoprotein E-deficient. *P < .05 compared with day 28 of AngII infusion; **P < .05 compared with sham. Journal of Vascular Surgery 2015 61, 767-776DOI: (10.1016/j.jvs.2013.11.004) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

Fig 2 Castration has no effect on abdominal aortic aneurysm (AAA) maximum external diameters from angiotensin II (AngII)-infused mice. A, Aortas from mice in each group that underwent whole-body perfusion fixation (n = 12/group). B, Maximal external diameters of suprarenal abdominal aortas are shown from sham-operated (n = 15) and castrated (n = 17) mice. Data are mean ± standard error of the mean (error bars). Journal of Vascular Surgery 2015 61, 767-776DOI: (10.1016/j.jvs.2013.11.004) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

Fig 3 Abdominal aortic aneurysms (AAAs) from castrated mice have increased vascular volume. A, A three-dimensional (3D) image of a representative AAA from a mouse in each group illustrates changes in aortic remodeling. B, Total volume (mm3) of AAAs in (A) imaged by ultrasound (n = 11 mice/group). C, Vascular volume/lumen volume ratio from AAAs imaged by ultrasound in mice from each group. The error bars indicate the standard error of the mean. *P < .05 compared with sham. Journal of Vascular Surgery 2015 61, 767-776DOI: (10.1016/j.jvs.2013.11.004) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

Fig 4 Abdominal aortic aneurysm (AAA) sections from castrated mice have increased smooth muscle α-actin immunostaining. AAA sections from (A and B) the proximal to (C and D) the distal end of AAA tissue sections from (A and C) sham-operated and (B and D) castrated mice were immunostained for smooth muscle α-actin. E, Quantification of α-actin immunostaining in AAA sections from each group exhibiting the largest luminal dilation. Data are mean ± standard error of the mean (error bars) from six AAAs per group. *P < .05 compared with sham. Journal of Vascular Surgery 2015 61, 767-776DOI: (10.1016/j.jvs.2013.11.004) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

Fig 5 Abdominal aortic aneurysm (AAA) sections from castrated mice have increased ground substance and collagen content. AAA sections from the proximal (top) to distal (bottom) end of AAA tissue sections from mice in each group were stained using Gömöri trichrome. Data are from six AAAs/group. Blue/green, collagen. Journal of Vascular Surgery 2015 61, 767-776DOI: (10.1016/j.jvs.2013.11.004) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

Fig 6 Castration has no effect on atherosclerosis in mice infused chronically with angiotensin II (AngII). Lesion surface area in the aortic arch was quantified by en face methods. The circles indicate individual mice, with diamonds indicating mean ± standard error of the mean (error bars) from 14 mice/group. Journal of Vascular Surgery 2015 61, 767-776DOI: (10.1016/j.jvs.2013.11.004) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

Fig 7 Testosterone reduces messenger RNA (mRNA) abundance of transforming growth factor-β1 (TGF-β1) and plasminogen activator inhibitor (PAI-1) in abdominal aortic smooth muscle cells. Cells were incubated with vehicle or testosterone for 12, 24, or 48 hours before quantification of mRNA abundance. Data are shown as the mean ± the standard error of the mean (error bars) as from three experiments. *P < .05 compared with vehicle. Journal of Vascular Surgery 2015 61, 767-776DOI: (10.1016/j.jvs.2013.11.004) Copyright © 2015 Society for Vascular Surgery Terms and Conditions