Differential Gender And Species Specific Formation of Aneurysms Using A Novel Method Of Inducing Abdominal Aortic Aneurysms

Laser, Adriana; Lu, Guanyi; Ghosh, Abhishek; Roelofs, Karen J.; McEvoy, Brendan; DiMusto, Paul D.; Bhamidipati, Castigliano M.; Ailawadi, Goarv; Eliason, J.L.; Henke, Peter K.; Upchurch, Gilbert R.

doi:10.1016/j.jss.2010.11.092

Cited by 7 publications

(11 citation statements)

References 8 publications

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“…Another study concluded that genetic susceptibility is important in AAA development, as significantly more macrophages were found in C57BL/6 male than female mice, but there was no difference between sexes in B6129 mice. 60 Moreover, similar to human AAA tissue, male mice had higher levels of p308 which was correlated with increased AAA formation compared with female mice. 39 Finally, Johnston et al 38 showed that the protective effects in female mice were completely eliminated with deletion of aromatase.…”

Section: Sex Differences In Aaa Animal Models the Role Of Endogenous mentioning

confidence: 88%

“…More recently, sex differences in AAA have been studied in different animal models, which include the intraluminal infusion of elastase in rats 57 or mice, 58 angiotensin II (AngII) infusion in mice deficient in apolipoprotein E (Apoe À/À ), 59 and direct application of elastase at the anterior wall of the abdominal aorta in mice (Table III). 60 In 2001, Lee et al 61 described an increased incidence of AAA in female mice deficient in the inducible form of nitric oxide synthase (Nos2 À/À ) compared with male mice (80% vs. 40%), suggesting that the interaction between estrogen and cellular NOS could influence nitric oxide production and that the absence of NOS2 might have enhanced local MMP9 activity and promoted aneurysmal degeneration in a sex-specific manner. Another study reported a higher incidence and a larger size of AAA in male than in female mice in Apoe…”

Section: Sex Differences In Aaa Animal Models the Role Of Endogenous mentioning

confidence: 99%

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Sex Differences in Abdominal Aortic Aneurysm: The Role of Sex Hormones

Makrygiannis

Courtois

Drion

et al. 2014

Annals of Vascular Surgery

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Abdominal aortic aneurysm (AAA) is a complex multifactorial disease with genetic and environmental components. AAA is more common in men, whereas women have a greater risk of rupture and more frequently have concomitant thoracic aortic aneurysms. Moreover, women are diagnosed with AAA about 10 years later and seem to be protected by female sex hormones. In this MEDLINE-based review of literature, we examined human and animal in vivo and in vitro studies to further deepen our understanding of the sexual dimorphism of AAA. We focus on the role of sex hormones during the formation and growth of AAA. Endogenous estrogens and exogenous 17b-estradiol were found to exert favorable actions protecting from AAA in animal models, whereas exogenous hormone replacement therapy in humans had inconclusive results. Androgens, known to have detrimental effects in the vasculature, in sufficient levels maintain the integrity of the aortic wall through their anabolic actions and act differentially in men and women, whereas lower levels of testosterone have been associated with AAA in humans. In conclusion, sex differences remain an important area of AAA research, but further studies especially in humans are needed. Furthermore, differential molecular mechanisms of sex hormones constitute a potential therapeutic target for AAA.

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Section: Sex Differences In Aaa Animal Models the Role Of Endogenous mentioning

confidence: 88%

Section: Sex Differences In Aaa Animal Models the Role Of Endogenous mentioning

confidence: 99%

Sex Differences in Abdominal Aortic Aneurysm: The Role of Sex Hormones

Makrygiannis

Courtois

Drion

et al. 2014

Annals of Vascular Surgery

View full text Add to dashboard Cite

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“…In experimental animal models of aneurysms such as the elastase-induced model (Laser, Lu et al 2012) and Angiotensin II-induced model (Daugherty and Cassis 2004) some development of ILT has been observed.…”

Section: Properties Of the Iltmentioning

confidence: 99%

Protease activity in the multi-layered intra-luminal thrombus of abdominal aortic aneurysms

et al. 2011

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“…Despite this, each model offers mechanistic and therapeutic insight into key pathological components associated with AAA development and progression. Given the importance of the adventitial layer and its vasa vasorum in mediating inflammatory cell infiltration 49,59,60 , we selected a topical elastase-based approach to experimentally induce aortic inflammation and subsequent expansion 61 . The resulting inflammatory cell infiltration from the vasa vasorum has been shown to mimic observations in human aneurysms 62–65 .…”

Section: Discussionmentioning

confidence: 99%

Human Adipose-Derived Stem Cells Suppress Elastase-Induced Murine Abdominal Aortic Inflammation and Aneurysm Expansion through Paracrine Factors

et al. 2017

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Abdominal aortic aneurysm (AAA) is a potentially lethal disease associated with immune activation-induced aortic degradation. We hypothesized that xenotransplantation of human adipose-derived stem cells (hADSCs) would reduce aortic inflammation and attenuate expansion in a murine AAA model. Modulatory effects of ADSCs on immune cell subtypes associated with AAA progression were investigated using human peripheral blood mononuclear cells (hPBMNCs) cocultured with ADSCs. Murine AAA was induced through elastase application to the abdominal aorta in C57BL/6 mice. ADSCs were administered intravenously, and aortic changes were determined by ultrasonography and videomicrometry. Circulating monocytes, aortic neutrophils, CD28- T cells, FoxP3+ regulatory T cells (Tregs), and CD206+ M2 macrophages were assessed at multiple terminal time points. In vitro, ADSCs induced M2 macrophage and Treg phenotypes while inhibiting neutrophil transmigration and lymphocyte activation without cellular contact. Intravenous ADSC delivery reduced aneurysmal expansion starting from day 4 [from baseline: 54.8% (saline) vs. 16.9% (ADSCs), n = 10 at baseline, n = 4 at day 4, p < 0.001], and the therapeutic effect persists through day 14 (from baseline: 64.1% saline vs. 24.6% ADSCs, n = 4, p < 0.01). ADSC administration increased aortic Tregs by 20-fold (n = 5, p < 0.01), while decreasing CD4+CD28- (-28%), CD8+CD28- T cells (-61%), and Ly6G/C+ neutrophils (-43%, n = 5, p < 0.05). Circulating CD115+CXCR1-LY6C+-activated monocytes decreased in the ADSC-treated group by day 7 (-60%, n = 10, p < 0.05), paralleled by an increase in aortic CD206+ M2 macrophages by 2.4-fold (n = 5, p < 0.05). Intravenously injected ADSCs transiently engrafted in the lung on day 1 without aortic engraftment at any time point. In conclusion, ADSCs exhibit pleiotropic immunomodulatory effects in vitro as well as in vivo during the development of AAA. The temporal evolution of these effects systemically as well as in aortic tissue suggests that ADSCs induce a sequence of anti-inflammatory cellular events mediated by paracrine factors, which leads to amelioration of AAA progression.

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Differential Gender And Species Specific Formation of Aneurysms Using A Novel Method Of Inducing Abdominal Aortic Aneurysms

Abstract: Background-The objective of this study was to test a novel model of inducing AAA in different mouse strains and genders.

Cited by 7 publications

References 8 publications

Sex Differences in Abdominal Aortic Aneurysm: The Role of Sex Hormones

Sex Differences in Abdominal Aortic Aneurysm: The Role of Sex Hormones

Protease activity in the multi-layered intra-luminal thrombus of abdominal aortic aneurysms

Human Adipose-Derived Stem Cells Suppress Elastase-Induced Murine Abdominal Aortic Inflammation and Aneurysm Expansion through Paracrine Factors

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