Castration of male mice prevents the progression of established angiotensin II-induced abdominal aortic aneurysms.

Castration of male mice prevents the progression of established angiotensin II-induced abdominal aortic aneurysms.
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DOI:
10.1016/j.jvs.2013.11.004
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发表时间:
2015-03
影响因子:
4.3
通讯作者:
Cassis, Lisa A.
Cassis, Lisa A.
中科院分区:
医学2区
文献类型:
--
作者:
Zhang, Xuan;Thatcher, Sean;Wu, Congqing;Daugherty, Alan;Cassis, Lisa A.

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男性是腹主动脉瘤(AAA)发展的不可改变的风险因素。与人类相似,雄性小鼠比雌性小鼠更容易受到血管紧张素II(AngII)诱导的AAA的影响。以前的研究表明,雄性去势显着减少血管紧张素II诱导的AAA的形成。AAA大小的进展与动脉瘤破裂风险增加相关。在这项研究中,我们假设雄性小鼠的去势会减少已建立的AngII诱导的AAA的进展。雄性载脂蛋白E(ApoE)-/-小鼠输注AngII 1个月以诱导AAA形成。通过超声测量主动脉直径,并将小鼠分为假手术组或去势组。AngII输注持续另外2个月。超声用于量化管腔直径,并对切除的腹主动脉瘤进行处理,以量化AAA大小、体积和组织特征。假手术小鼠在持续AngII输注期间表现出肾上主动脉腔直径的进行性扩张。去势显著降低了主动脉腔直径(研究终点:1.88 ± 0.05 mm vs 1.63 ± 0.04 mm; P<0.05;假手术组[n = 15] vs去势组[n = 17])。然而,最大外部AAA直径假手术和去势小鼠之间没有显着差异。通过超声成像的切除的AAA的血管体积/管腔体积比通过去势显著增加(假手术,4.8 ± 0.9;去势,9.5 ± 2.0%; n = 11/组; P<0.05)。此外,与假手术小鼠的薄壁AAA相比,去势小鼠的动脉瘤切片显示平滑肌肌动蛋白和胶原蛋白增加。通过去势去除内源性雄性激素选择性地减少主动脉腔扩张,同时不改变外部AAA尺寸。
Male sex is a non-modifiable risk factor for abdominal aortic aneurysm (AAA) development. Similar to humans, male mice are more susceptible to angiotensin II (AngII)-induced AAAs than females. Previous studies demonstrated that castration of males markedly reduced the formation of AngII-induced AAAs. Progression of AAA size is associated with increased risk of aneurysm rupture. In this study, we hypothesized that castration of male mice would reduce the progression of established AngII-induced AAAs. Male apolipoprotein E (ApoE)-/- mice were infused with AngII for 1 month to induce AAA formation. Aortic diameters were measured by ultrasound and mice were stratified into 2 groups that were either sham-operated or castrated. AngII infusions were continued for a further 2 months. Ultrasound was used to quantify lumen diameters, and excised aortas were processed for quantification of AAA size, volume, and tissue characteristics. Sham-operated mice exhibited progressive dilation of suprarenal aortic lumen diameters during continued AngII infusion. Castration significantly decreased aortic lumen diameters (study endpoint: 1.88 ± 0.05 mm vs 1.63 ± 0.04 mm; P<.05; sham-operated [n = 15] vs castration [n = 17], respectively). However, maximal external AAA diameters were not significantly different between sham-operated and castrated mice. The vascular volume/lumen volume ratio of excised AAAs imaged by ultrasound was significantly increased by castration (sham-operated, 4.8 ± 0.9; castration, 9.5 ± 2.0 %; n = 11/group; P<.05). Moreover, compared to thin walled AAAs of sham-operated mice, aneurysm sections from castrated mice exhibited increased smooth muscle -actin and collagen. Removal of endogenous male hormones by castration selectively reduces aortic lumen expansion while not altering the external AAA dimensions.
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