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Aromatase is required for female abdominal aortic aneurysm protection

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Presentation on theme: "Aromatase is required for female abdominal aortic aneurysm protection"— Presentation transcript:

1 Aromatase is required for female abdominal aortic aneurysm protection
William F. Johnston, MD, Morgan Salmon, PhD, Gang Su, MD, Guanyi Lu, MD, PhD, Gorav Ailawadi, MD, Gilbert R. Upchurch, MD  Journal of Vascular Surgery  Volume 61, Issue 6, Pages e4 (June 2015) DOI: /j.jvs Copyright © 2015 Society for Vascular Surgery Terms and Conditions

2 Fig 1 Confocal immunohistochemistry staining for nuclei (DAPI), smooth muscle cells (smooth muscle α-actin [SMαA]), macrophages (CD68 in human and Mac-2 in mouse), and aromatase in human (A) and mouse (B) abdominal aortic aneurysm (AAA) cross sections. In both human and mouse AAAs, aromatase co-localized to cells with SMαA and macrophage markers. A, A sample of medial layer of human AAA. B, Lumen, media, and adventitia of mouse AAA. Scale bar = 10 μm. Journal of Vascular Surgery  , e4DOI: ( /j.jvs ) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

3 Fig 2 Aortic dilation (black line) increased over time after elastase exposure. However, aortic aromatase expression (red line) remained constant and did not differ in response to elastase perfusion. AAA, Abdominal aortic aneurysm. Journal of Vascular Surgery  , e4DOI: ( /j.jvs ) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

4 Fig 3 In vitro measurement of estradiol levels in aortas of mice with aromatase (wild type: WT) and without aromatase (ArKO) treated with testosterone or control solution. Estradiol levels were significantly increased in WT aortas exposed to testosterone compared with aortas with aromatase deletion or aortas exposed to only control solution without testosterone. ***P < Journal of Vascular Surgery  , e4DOI: ( /j.jvs ) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

5 Fig 4 A, Maximal aortic dilation of male (M) and female (F) mice with and without aromatase (WT and ArKO) demonstrating a significant reduction in aortic dilation in female mice with aromatase compared with male mice. Female ArKO mice had increased aortic dilation compared with female WT mice and were similar to male mice. B, Maximal aortic dilation of female wild-type mice with aromatase (Ar+/+, WT), heterozygous deletion of aromatase (Ar+/−), and complete deletion of aromatase (Ar−/−, KO) demonstrating a progressive increase in aortic dilation with increased aromatase deletion. **P < .005; ***P < Journal of Vascular Surgery  , e4DOI: ( /j.jvs ) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

6 Fig 5 A, Comparison of maximal aortic dilation of female wild-type mice with aromatase with ovaries (F WT), female wild-type mice after ovariectomy (F WT ovx), and female mice without aromatase after ovariectomy (F ArKO ovx).*P < .05, ***P < B, Representative aortic cross sections stained for macrophages (Mac-2, brown), neutrophils (Ly6B, brown), smooth muscle cells (smooth muscle α-actin antibody [SMαA], brown), and elastin fibers (Verhoeff–van Gieson, black). Scale bar = 50 μm. Journal of Vascular Surgery  , e4DOI: ( /j.jvs ) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

7 Fig 6 Cytokine protein array comparing monocyte chemoattractant protein 1 (MCP-1) levels (A) and interleukin-1β (IL-1β) levels (B) from isolated protein from female wild-type mice (F WT), female wild-type mice after ovariectomy (F WT ovx), and female mice without aromatase or ovaries (F ArKO ovx). *P < .05; ***P < Journal of Vascular Surgery  , e4DOI: ( /j.jvs ) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

8 Fig 7 Circulating estradiol levels (A) and testosterone levels (B) from serum at 14 days after elastase perfusion in female wild-type mice (F WT), female wild-type mice after ovariectomy (F WT ovx), female mice with aromatase deletion (F ArKO), and female mice with aromatase deletion after ovariectomy (F ArKO ovx). The dashed line represents the lower limit of detection for the assay. C, Correlation of aortic dilation with serum circulating estradiol levels. R, Pearson correlation coefficient. Journal of Vascular Surgery  , e4DOI: ( /j.jvs ) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

9 Supplementary Fig 1 (online only)
Comparison of baseline aortic diameter in female wild-type mice with aromatase with ovaries (F WT), female wild-type mice after ovariectomy (F WT ovx), and female mice without aromatase after ovariectomy (F ArKO ovx) demonstrated no significant differences in baseline aortic size. P = .36 (nonsignificant by analysis of variance). Journal of Vascular Surgery  , e4DOI: ( /j.jvs ) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

10 Supplementary Fig 2 (online only)
Complete cytokine array for aortas of female wild-type mice (F WT), female wild-type mice after ovariectomy (F WT ovx), and female mice with aromatase deletion (F ArKO). CXCL, C-X-C motif ligand chemokine; C5, complement component 5; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; CCL, C-C motif ligand chemokine; CD54, cluster of differentiation 54; INF-γ, interferon-γ; IL, interleukin; M-CSF, macrophage colony-stimulating factor; MCP-1, monocyte chemotactic protein 1; MIP, macrophage inflammatory protein; RANTES, regulated on activation, normal Tcell expressed and secreted; SDF, stromal cell–derived factor; TARC, thymus- and activation-regulated chemokine; TIMP, tissue inhibitor of metalloproteinase; TNF-α, tumor necrosis factor-α; TREM, triggering receptor expressed on myeloid cells. *P < .05; **P < .005; ***P < Journal of Vascular Surgery  , e4DOI: ( /j.jvs ) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

11 Supplementary Fig 2 (online only)
Complete cytokine array for aortas of female wild-type mice (F WT), female wild-type mice after ovariectomy (F WT ovx), and female mice with aromatase deletion (F ArKO). CXCL, C-X-C motif ligand chemokine; C5, complement component 5; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; CCL, C-C motif ligand chemokine; CD54, cluster of differentiation 54; INF-γ, interferon-γ; IL, interleukin; M-CSF, macrophage colony-stimulating factor; MCP-1, monocyte chemotactic protein 1; MIP, macrophage inflammatory protein; RANTES, regulated on activation, normal Tcell expressed and secreted; SDF, stromal cell–derived factor; TARC, thymus- and activation-regulated chemokine; TIMP, tissue inhibitor of metalloproteinase; TNF-α, tumor necrosis factor-α; TREM, triggering receptor expressed on myeloid cells. *P < .05; **P < .005; ***P < Journal of Vascular Surgery  , e4DOI: ( /j.jvs ) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

12 Supplementary Fig 2 (online only)
Complete cytokine array for aortas of female wild-type mice (F WT), female wild-type mice after ovariectomy (F WT ovx), and female mice with aromatase deletion (F ArKO). CXCL, C-X-C motif ligand chemokine; C5, complement component 5; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; CCL, C-C motif ligand chemokine; CD54, cluster of differentiation 54; INF-γ, interferon-γ; IL, interleukin; M-CSF, macrophage colony-stimulating factor; MCP-1, monocyte chemotactic protein 1; MIP, macrophage inflammatory protein; RANTES, regulated on activation, normal Tcell expressed and secreted; SDF, stromal cell–derived factor; TARC, thymus- and activation-regulated chemokine; TIMP, tissue inhibitor of metalloproteinase; TNF-α, tumor necrosis factor-α; TREM, triggering receptor expressed on myeloid cells. *P < .05; **P < .005; ***P < Journal of Vascular Surgery  , e4DOI: ( /j.jvs ) Copyright © 2015 Society for Vascular Surgery Terms and Conditions

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